@article {pmid41618017,
year = {2026},
author = {Beccherle, M and Amato, S and Facci, E and Stefanescu, G and Bertagnoli, S and Francesco, VD and Fontana, G and Gambina, G and Moro, V},
title = {Patterns of cognitive and motor decline in Alzheimer's Disease (AD) and ageing in healthy populations.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-026-03327-1},
pmid = {41618017},
issn = {1720-8319},
}

@article {pmid41617942,
year = {2026},
author = {Ran, Z and Yang, LL and Zhou, LY and Wen, T and Wang, WJ and Chen, L},
title = {Research trends and hotspots of nanomaterials in Alzheimer's disease: bibliometric analysis.},
journal = {Discover nano},
volume = {21},
number = {1},
pages = {20},
pmid = {41617942},
issn = {2731-9229},
support = {82204761//National Natural Science Foundation of China/ ; 2024SZY120//the Deyang Science and Technology Bureau/ ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited clinical treatment options. Nanoparticle technology offers promising new strategies for innovative diagnosis and therapy of AD. However, the rapid development of this field has not been accompanied by a systematic bibliometric analysis. This study applies bibliometric methods to comprehensively evaluate the development trends and prospects of nanoparticle applications in AD research.

MATERIALS AND METHODS: Publications related to nanomaterials in AD were retrieved from the Web of Science Core Collection. Visualization and analysis were conducted using VOSviewer, CiteSpace, and the Bibliometrix package in R to identify research hotspots in the field.

RESULTS: A total of 2837 publications were included, involving 92 countries/regions, 2953 institutions, and 13,294 authors. China, the Chinese Academy of Sciences, and Xiao-Gang Qu were the most productive country, institution, and author, respectively. The Journal of Controlled Release was the most influential. Among them, Saraiva et al. (J Control Release 235:34-47, 2016) ranked first with 1069 citations, and their research highlights the great potential of nanoparticle drug delivery technology to cross the blood-brain barrier. Emerging keyword trends indicate a shift in research focus toward nasal delivery, extracellular vesicles, graphene quantum dots for diagnostics, and nanostructured lipid carriers for therapy.

CONCLUSION: Nanomaterial-based AD research is expanding rapidly. Current focus involves developing targeted nanoparticle systems to overcome the blood-brain barrier, mitigate Aβ pathology, and enable early diagnosis. Future work should prioritize mechanistic studies and clinical trials to translate potential into practical applications.},
}

@article {pmid41617706,
year = {2026},
author = {Johnson, LA and Saito, K and Pallerla, AV and Funnell, JL and Ezzo, AR and Song, CM and Harrison, DA and Norton, NJ and Moore, LC and Van Eldik, LJ and Fardo, DW and Cooper, GE and Morganti, JM},
title = {Clonal expansion of cytotoxic CD8[+] T cells in lecanemab-associated ARIA.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68921-3},
pmid = {41617706},
issn = {2041-1723},
support = {RF1NS118558//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; P20GM148326//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; P20GM148326//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; ABA-25-1376140/ALZ/Alzheimer's Association/United States ; ABA-25-1376140/ALZ/Alzheimer's Association/United States ; R01AG080589//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; TL1TR001997//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; },
abstract = {Amyloid-related imaging abnormalities (ARIA) are the principal safety concern limiting anti-amyloid therapies for Alzheimer's disease, yet their biology remains unclear. Here we show, through multi-omic profiling of peripheral blood from three ARIA+ patients and matched controls, that ARIA is associated with coordinated reprogramming of CD8 + T cells. CD8+ effector memory (TEM) and terminally differentiated (TEMRA) subsets were expanded, clonally enriched, and transcriptionally primed for cytotoxicity and vascular trafficking. Transcription factor inference and metabolomics converged on glycolytic reprogramming favoring short-lived effector function. Ligand-receptor modeling revealed enhanced monocyte-to-T cell signaling through antigen presentation, adhesion, and chemokine axes, while integration with a cerebrovascular atlas confirmed that ARIA-associated TEMRAs are transcriptionally "addressed" for vascular engagement. Together, these findings identify a peripheral immune signature linking metabolic reprogramming, clonal CD8+ expansion, and altered intercellular communication to ARIA, with implications for biomarker development and risk mitigation pending validation in larger cohorts.},
}

@article {pmid41617662,
year = {2026},
author = {Zhang, C and Zuo, Y and Ning, Q and Yuan, S and Deng, Z and Yin, H and Zhao, A},
title = {XRepDDA: An Interpretable Drug-Disease Association Prediction Framework Leveraging Pretrained Chemical Language Models.},
journal = {Journal of chemical information and modeling},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jcim.5c02901},
pmid = {41617662},
issn = {1549-960X},
abstract = {Drug repositioning aims to identify new indications for existing drugs, offering a cost-effective and time-efficient strategy for therapeutic development. Its core challenge lies in accurately predicting potential drug-disease associations (DDAs). However, existing computational approaches often suffer from inadequate drug representation, insufficient modeling of disease semantics, and imbalanced data distributions, which collectively limit predictive accuracy and generalization ability. To address these challenges, we propose an innovative framework, termed XRepDDA, that integrates multimodal feature representation with deep metric learning to improve DDA prediction accuracy and robustness. For drug representation, the SMI-TED pretrained chemical language model encodes SMILES sequences into chemically informative molecular embeddings. For disease representation, a hierarchical semantic graph based on the MeSH ontology is constructed together with a semantic-enhanced graph embedding strategy to capture hierarchical and semantic relationships among diseases. To mitigate class imbalance, we applied the AllKNN adaptive undersampling strategy. The prediction module is built upon an improved ModernNCA architecture, which learns a discriminative embedding space through deep metric learning. Experiments on multiple public benchmark data sets demonstrate that XRepDDA consistently outperforms diverse baseline models, including traditional machine learning, tree-based ensemble, and deep learning methods, achieving AUC and AUPR values of up to 0.9990 and 0.9991, respectively. Furthermore, molecular docking experiments on top-ranked candidate drugs for Alzheimer's disease and stomach neoplasms provide in silico validation of predictive reliability. To enhance interpretability, a multilevel explainability framework is established, combining SHAP-based global feature attribution with attention mechanisms and molecular perturbation analyses to identify key features and pharmacophores at the local level. These results support the chemical interpretability and the biological plausibility of the predictions.},
}

@article {pmid41617635,
year = {2026},
author = {Michopoulou, S and Prosser, A and O'Brien, N and Dickson, J and Guy, M and Teeling, JL and Kipps, CM},
title = {Alzheimer's disease diagnosis support for brain perfusion SPECT scans in a real-world clinical cohort.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251413790},
doi = {10.1177/13872877251413790},
pmid = {41617635},
issn = {1875-8908},
abstract = {BackgroundDementia diagnosis is challenging and often delayed. Brain imaging techniques such as single-photon emission computed tomography (SPECT) imaging can help identify subtle changes in brain perfusion. Artificial intelligence methods may support results interpretation for early diagnosis.ObjectiveTo develop and validate multivariate models for the early diagnosis of Alzheimer's disease (AD), using brain perfusion SPECT imaging and interpretable artificial intelligence methods in a real-world clinical setting.MethodsTwo logistic regression models were developed using a training dataset of 420 SPECT scans and tested on an independent clinical dataset of 443 scans. Model 1 was designed to identify abnormal perfusion patterns, while Model 2 identified perfusion changes associated with AD. Input features were extracted from anatomical volumes of interest, with feature selection performed using the Minimum Redundancy Maximum Relevance (MRMR) algorithm.ResultsThe models demonstrated good classification performance using real-world clinical data. Model 1 achieved an area under receiver operator characteristic (AUROC) Curve of 0.89 (Sensitivity 76%, Specificity 87%) in identifying abnormal brain perfusion. Model 2 achieved an AUROC of 0.86 (Sensitivity 87%, Specificity 72%) in identifying AD.ConclusionsMultivariate logistic regression models trained on real-world clinical data show promise as clinical decision support tools for the diagnosis of AD from brain perfusion SPECT imaging. The models use features from clinically relevant brain regions, which enhances interpretability. Future research should focus on expanding model applicability to other dementia types and on prospective evaluation of their utility in improving diagnostic accuracy, consistency, and care pathways in diverse clinical environments.},
}

@article {pmid41617141,
year = {2026},
author = {Grady, A and Stinchcombe, A},
title = {Associations Between Cognitive Risk Scores and Objective Cognition by Sexual Orientation: Evidence From the CLSA.},
journal = {Research on aging},
volume = {},
number = {},
pages = {1640275261417696},
doi = {10.1177/01640275261417696},
pmid = {41617141},
issn = {1552-7573},
abstract = {This study investigated differences in cognitive risk and objective cognitive performance between lesbian, gay, and bisexual (LGB; n = 309) and heterosexual (n = 16,207) older adults using baseline data (2011-2015) from the Comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA). Cognitive risk was assessed using the Australian National University - Alzheimer's Disease Risk Index (ANU-ADRI). Cognitive performance was measured using a composite score based on performance on six cognitive tests. The analytic strategy included a combination of t-tests, chi-square tests, and linear regression models. Contrary to expectations, LGB participants exhibited lower cognitive risk scores (M = -1.08, SD = 8.85) in comparison to heterosexual participants (M = 0.61, SD = 10.62). On subcomponents of the ANU-ADRI score, LGB participants reported higher rates of depression and smoking, and lower social engagement. In terms of cognitive performance, LGB participants scored significantly higher (M = 104.58, SD = 14.72) in comparison to heterosexual participants (M = 100.12, SD = 15.05). This difference remained even after controlling for ANU-ADRI score, race, and income. Our findings highlight the importance of incorporating sociodemographic characteristics into cognitive risk assessments.},
}

@article {pmid41617088,
year = {2026},
author = {Sala-Vila, A and Tintle, N and Westra, J and DeJong, E and Clark, T and Miller, P and Belury, MA and Harris, WS},
title = {Plasma n6 polyunsaturated fatty acid levels and risk for dementia: A prospective observational study from the UK Biobank.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {101220},
doi = {10.1016/j.ajcnut.2026.101220},
pmid = {41617088},
issn = {1938-3207},
abstract = {BACKGROUND: Some recent observational studies have linked higher blood linoleic acid (LA) with lower risk of cardiometabolic diseases. However, these associations have not been observed for other n-6 polyunsaturated fatty acids (PUFAs) which, in some settings have been linked to higher disease risk, and thus the controversy over the health effects of n-6 PUFAs remains. Dementia is a paradigmatic case of it.

OBJECTIVES: To investigate the association of linoleic acid and non-LA n-6 PUFAs with the risk of incident dementia.

METHODS: We included 273,795 participants from the UK Biobank free of dementia at baseline for whom plasma n-6 PUFAs data were available. We modeled the relationships between LA and, separately, non-LA n-6 PUFAs and incident dementia by quintile (Q) and using continuous linear model using Cox proportional hazards models adjusting for variables reported to relate to incident dementia.

RESULTS: A total of 5,799 incident dementia cases were ascertained (median follow-up: 15.06 years; 25[th] and 75[th] percentiles: 14.22-15.80 years). Compared to participants at Q1 (lowest quintile) of LA, those at Q5 (highest quintile) showed a lower risk of dementia (adjusted hazard ratio [95% confidence interval] = 0.82 [0.74, 0.91]). In contrast, participants at Q5 of plasma non-LA n-6 PUFAs were at a higher risk of incident dementia when compared to Q1 (1.21 [1.10, 1.33]). Similar patterns were observed when considering LA and non-LA n-6 PUFAs continuously.

CONCLUSIONS: We observed heterogeneous associations between different types of n-6 PUFAs and risk of dementia, supporting the increasing view that n-6 PUFAs should not be treated homogeneously. Future research should investigate whether dietary LA (which drives plasma LA levels) may help reduce risk for dementia.

REGISTRATION: This research has been conducted using the UK Biobank Resource under Application Number 85092.},
}

@article {pmid41617047,
year = {2026},
author = {Hu, J and Wang, WX},
title = {DNA Methylation-Mediated Alterations in Copper(I/II) Redox Equilibrium Underlie Lead-Induced Neurotoxicity.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127739},
doi = {10.1016/j.envpol.2026.127739},
pmid = {41617047},
issn = {1873-6424},
abstract = {Lead (Pb), a ubiquitous environmental toxin, poses significant risks to central nervous system health, primarily by disrupting essential metal homeostasis in the brain. While epigenetic regulation and proteomic expression are significantly affected by Pb, its specific molecular impact on copper (Cu) redox states remains poorly understood. This study systematically investigated the molecular mechanisms underlying Pb-induced neurotoxicity in SH-SY5Y cells through integrated epigenomics and proteomics analysis. DNA methylation analysis revealed 141,357 differentially methylated regions (DMRs), primarily in CpG sites, with 62.6% hypermethylated and 37.4% hypomethylated. These DMRs were enriched in genes associated with critical processes such as metal ion binding, cell cycle regulation, and nervous system development. Promoter-specific methylation changes were notably pronounced, impacting pathways linked to neurodegenerative diseases, including Alzheimer's disease. Proteomic analysis identified 740 differentially expressed proteins (DEPs), with 366 upregulated and 374 downregulated in Pb-treated cells. Functional annotation revealed significant enrichment of DEPs in mitochondria, where Pb exposure disrupted processes related to oxidative phosphorylation, ion transport, and transmembrane processes. These proteomic changes aligned with the observed epigenetic modifications, reinforcing the role of Pb in impairing neuronal function via its effects on cellular energy metabolism and metal ion dynamics. Notably, Pb exposure disrupted Cu redox transitions between Cu(I) and Cu(II) as well as glutathione (GSH) activity, underscoring its impact on cellular metal homeostasis regulation and oxidative imbalance. In summary, this study provides a comprehensive view of how Pb exposure alters epigenetic and proteomic landscapes, disrupting key biological processes and pathways essential for neuronal health.},
}

@article {pmid41617020,
year = {2026},
author = {Liao, J and Huang, Q and Li, R and Gong, L and Li, T and Lin, Z},
title = {Long-acting nanomedicine for brain diseases.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {114665},
doi = {10.1016/j.jconrel.2026.114665},
pmid = {41617020},
issn = {1873-4995},
abstract = {Effective pharmacological management of neurological disorders is profoundly limited by the blood-brain barrier (BBB) and the short biological half-life of therapeutics, necessitating frequent and invasive administration. Long-acting drug delivery systems (LADDS) integrated with nanotechnology offer a transformative paradigm to overcome these challenges. This review discusses the key principles and nanoplatforms enabling sustained brain drug delivery to the central nervous system. Key release mechanisms are analyzed including diffusion, degradation, and stimuli-responsiveness which alongside a survey of major nanocarrier platforms, designed to achieve controlled pharmacokinetics and enhanced BBB penetration. Recent groundbreaking applications in preclinical models of ischemic stroke, Alzheimer's disease, glioma, and traumatic brain injury are highlighted, where LADDS provide continuous, localized neuroprotection and modulate chronic pathology. Finally, the significant translational challenges, including long-term biocompatibility, manufacturing scalability, and regulatory hurdles, are critically evaluated. The future trajectory of the field points toward intelligent and personalized systems, integrating AI-driven design, bioresponsive materials, refillable depots, and bioelectronic hybrids. LADDS are poised to redefine neuropharmacology, shifting the focus from transient symptom management to precise, durable, and restorative intervention for chronic brain diseases.},
}

@article {pmid41617015,
year = {2026},
author = {Zhai, Z and Wang, W and Wang, G and Wei, C and Wei, S and Li, J and Zheng, L and Yue, X and Chen, C and Jiang, J and Zhu, B and Zhao, Z and Pan, X and Wu, C and Zhang, X},
title = {Rationalizing nose-to-brain drug delivery: Machine learning-guided optimization and mechanistic elucidation of olfactory deposition for nasal sprays.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {114667},
doi = {10.1016/j.jconrel.2026.114667},
pmid = {41617015},
issn = {1873-4995},
abstract = {Nose-to-brain drug delivery via nasal sprays is severely limited by low olfactory deposition. In this study, we integrate machine learning with high-throughput experimentation to systematically optimize olfactory deposition of solid lipid nanoparticle-loaded nasal sprays (SLN-NS). By engineering the dispersed medium properties using five excipients at varying concentrations across 40 formulations, we establish a three-level interlocking correlation among dispersed medium properties, spray performance, and olfactory deposition. We demonstrate that basic physicochemical properties predominantly influence microscopic droplet characteristics, while dynamic rheological parameters dictate macroscopic spray morphology. A random forest model accurately predicted olfactory deposition and guided the design of an optimized formulation, achieving 19.77% olfactory deposition, representing a 4 to 20-fold improvement over conventional nasal sprays. In vivo studies confirmed enhanced brain delivery and superior therapeutic efficacy in animal models of migraine, Alzheimer's, and Parkinson's diseases. This work provides a rational framework for optimizing nasal spray formulations to overcome anatomical barriers for improved CNS drug delivery.},
}

@article {pmid41616952,
year = {2026},
author = {Denver, P and Duffy, A and Kennedy, RT and Gault, VA and McClean, PL},
title = {Therapeutic efficacy of synthetic analogues of gut hormones in a mouse model of Alzheimer's disease.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.01.038},
pmid = {41616952},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is a neurodegenerative condition characterised by amyloid-β pathology, neuroinflammation, synaptic dysfunction and cognitive decline. Few pharmacological interventions are available, offering only symptomatic relief, and approval for a number of anti-amyloid biologics is limited, with concerns about safety, cost and efficacy. Here we investigated the effects of 8-10 weeks treatment with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], long-lasting analogues of gut hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and xenin-25, respectively, in the APP/PS1 mouse model of AD. Cognitive function was measured in novel object recognition (NOR) and Morris water maze (MWM) tasks and amyloid burden, gliosis, synapse density and neurogenesis were assessed in brains of APP/PS1 and wild-type mice. AD-associated gene expression analysis was performed to identify potential pathways targeted by treatment. Liraglutide and NAcGIP[Lys(37)PAL] improved cognitive performance in APP/PS1 mice and, along with Xenin-25[Lys(13)PAL], reduced amyloid-β burden in the brain. Liraglutide ameliorated gliosis and all three treatments restored synaptophysin levels. Additionally, Xenin-25[Lys(13)PAL] increased neurogenesis in the dentate gyrus. Numerous AD-associated genes were altered in the brain following treatments. Notably, Serpina3c was upregulated in brains of APP/PS1 mice treated with liraglutide, NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL], while Map2, Adam9, Lrp8, Casp3, Abca1 and App were downregulated. These results underscore the neuroprotective effects of liraglutide and suggest that NAcGIP[Lys(37)PAL] and Xenin-25[Lys(13)PAL] possess neuroprotective properties. Further investigation of the precise nature of these effects may support development of multi-target therapeutics based on combinations of gut hormone analogues.},
}

@article {pmid41616931,
year = {2026},
author = {Licciardo, D and Matti, C and Benelli, A and Isella, V and Appollonio, I and Santarnecchi, E},
title = {Gray matter atrophy and structural connectivity in Posterior Cortical Atrophy: a voxel-based meta-analysis.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106554},
doi = {10.1016/j.neubiorev.2026.106554},
pmid = {41616931},
issn = {1873-7528},
abstract = {Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome most commonly associated with Alzheimer's disease, characterized by progressive visuospatial and visuoperceptual decline. Although voxel-based morphometry studies have described gray matter loss in PCA, a comprehensive and updated coordinate-based meta-analysis is still missing, and associated structural connectivity alterations remain unclear. We conducted a systematic review and meta-analysis of whole-brain voxel-based morphometry studies comparing patients with PCA and healthy controls (PROSPERO ID: CRD420251010673). Analyses were performed using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) with family-wise error correction, and meta-regressions assessed the impact of demographic and clinical variables. To investigate structural connectivity, deterministic tractography was carried out on a normative diffusion MRI template, using meta-analytic gray matter clusters as seeds. Eighteen studies were included (339 PCA; 577 healthy controls). The meta-analysis revealed consistent bilateral gray matter atrophy in the lateral occipital cortex, inferior parietal lobule, precuneus, and ventral occipitotemporal regions. Meta-regression highlighted an interaction between age and disease duration, associated with atrophy in the left superior temporal gyrus and right thalamus. Tractography demonstrated that affected clusters were embedded within major long-range pathways, including the superior and inferior longitudinal fasciculi, vertical occipital fasciculi, and parietal aslant tract. Regression-derived clusters additionally mapped onto the arcuate fasciculus, frontal aslant tract, and superior thalamic radiations. This is the first systematic review and voxel-based meta-analysis of PCA conducted after the establishment of consensus diagnostic criteria, providing a statistically robust characterization of gray and white matter alterations and identifying potential imaging biomarkers for diagnosis and treatment.},
}

@article {pmid41616925,
year = {2026},
author = {Lanzillotta, S and Boccardi, V and Zulli, B and Napoli, A and Paolozzi, G and Angelini, R and Ruzicka, B and Fratini, F and Guazzarini, AG and Scamosci, M and Bastiani, P and Alunno, M and Westman, E and Di Domenico, F and Perluigi, M and Tramutola, A and Cecchetti, R and Mazza, T and Butterfield, DA and Mecocci, P and Barone, E},
title = {GDF-11, GDF-15, Jag-1, and leptin in neuronal-derived extracellular vesicles as aging-related biomarkers to identify individuals at risk of Alzheimer's dementia: A pilot study.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107291},
doi = {10.1016/j.nbd.2026.107291},
pmid = {41616925},
issn = {1095-953X},
abstract = {Aging is the strongest risk factor for Alzheimer's disease (AD). Identifying reliable biomarkers of brain aging helps to predict functional decline and dementia onset. Evaluations of aging-related biomarkers in plasma and neuronal-derived extracellular vesicles (nEVs) from cognitively healthy and AD subjects, alongside post-mortem IPL brain samples from control (Ctr), pre-clinical AD (PCAD), mild cognitive impairment (MCI) and AD cases were performed. Cognitive tests, functional assessments, and MRI data were also included. Biomarkers in nEVs more accurately reflected brain pathology than those measured in plasma and showed stronger associations with cognitive and functional decline. Sex-specific patterns also emerged: GDF-15 was higher in nEVs from females with AD, whereas IL-6, IL-18 and Jag-1 were higher in nEVs from males with AD. A minimal nEV-derived panel including lower GDF-11 and higher GDF-15, Jag-1 and Leptin (after correction for age and sex) discriminated AD from Ctr and was associated with MRI-determined cortical atrophy in regions vulnerable to AD. These markers captured aging-related molecular trajectories that were disrupted in AD, and key associations observed in nEVs were confirmed in post-mortem brain tissue. Our results suggests that nEV-derived biomarkers capture early, brain-specific and sex-modulated aging signatures, providing superior sensitivity compared to plasma. Their convergence with post-mortem findings underscores their biological validity and translational potential. These results highlight the value of nEVs for stratifying individuals at higher risk of AD and support their integration into precision medicine approaches for dementia prevention.},
}

@article {pmid41616912,
year = {2026},
author = {Wang, Z and Feng, W and Li, X and Yun, X and Wu, S and Du, L and Wang, H},
title = {Targeting the Nrf2/HO-1 aixs: a therapeutic strategy against regulated cell death in Alzheimer's disease.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103035},
doi = {10.1016/j.arr.2026.103035},
pmid = {41616912},
issn = {1872-9649},
abstract = {Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque deposition, neurofibrillary tangles of hyperphosphorylated tau protein, chronic neuroinflammation, and dysregulation of multiple regulated cell death pathways. Aging, as the primary risk factor for AD, is accompanied by the accumulation of oxidative stress, which serves as a pivotal contributor to AD pathogenesis and is intricately linked to the activation of diverse cell death modalities, including ferroptosis, pyroptosis, apoptosis, and autophagy-endoplasmic reticulum stress. The transcription factor nuclear factor erythroid 2-related factor 2(Nrf2) acts as a master regulator of cellular redox homeostasis. By binding to the antioxidant response element(ARE), Nrf2 orchestrates the transcriptional activation of a cytoprotective gene network, including heme oxygenase-1(HO-1). Activation of the Nrf2/HO-1 signaling axis not only enhances cellular antioxidant defenses but also critically regulates iron metabolism, suppresses inflammatory cascades, mitigates endoplasmic reticulum stress (ERS), and modulates autophagic and apoptotic processes. This review delineates the interplay between distinct cell death modalities in AD and their convergence with age-associated oxidative stress. It provides a comprehensive analysis of the neuroprotective mechanisms mediated by the Nrf2/HO-1 pathway in counteracting ferroptosis, pyroptosis, apoptosis and autophagic endoplasmic reticulum stress dysregulation. Furthermore, we discuss the therapeutic potential of pharmacologically targeting this pathway with various bioactive compounds, highlighting promising strategies for multi-targeted intervention in AD, particularly in the context of aging.},
}

@article {pmid41616780,
year = {2026},
author = {Kumar, M and Schlaffner, CN and Tang, S and Beuvink, MA and Viode, A and Mair, W and Jha, M and Uncu, C and Wesseling, H and Wang, T and Oakley, DH and Beerepoot, P and Xue, J and Connors, TR and Davis, DA and Frosch, MP and Murray, ME and Spina, SE and Grinberg, LT and Seeley, WW and Miller, BL and Boxer, AL and Geschwind, DH and Kosik, KS and Dickson, DW and Renard, BY and DeTure, M and McKee, AC and Hyman, BT and Steen, H and Steen, JA},
title = {Molecular features of human pathological tau distinguish tauopathy-associated dementias.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.12.036},
pmid = {41616780},
issn = {1097-4172},
abstract = {In Alzheimer's disease (AD), pathological tau protein shows a progressive accumulation of post-translational modifications (PTMs), reflecting disease severity, progression, and prion-like activity. Although many neurodegenerative diseases with dementia display tau aggregates, the pathological proteoforms of tau protein from each disease type remain unknown. Here, using a quantitative mass spectrometry-based proteomics platform, FLEXITau, deep characterization of pathological tau protein isolated from the brains of 203 human subjects with AD, familial AD (fAD), chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD), Pick's disease (PiD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB)-a non-tauopathy symptomatic control-and healthy controls (CTR) is performed. Unsupervised data analyses and supervised machine learning identify distinct molecular features of pathological tau for each disease, enabling molecular disease stratification. This study identifies potential disease-specific biomarkers and therapeutic targets for tauopathies and provides critical quantitative information for pharmacokinetic modeling required for therapeutic and disease mechanism studies.},
}

@article {pmid41616770,
year = {2026},
author = {Shipley, S and Abrate, MP and Hayman, R and Chan, D and Barry, C},
title = {Disrupted hippocampal replay is associated with reduced offline map stabilization in an Alzheimer's mouse model.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2025.12.061},
pmid = {41616770},
issn = {1879-0445},
abstract = {Alzheimer's disease is characterized by progressive memory decline associated with hippocampal degeneration. However, the specific physiological mechanisms underlying hippocampal dysfunction in the disease remain poorly understood-improved knowledge may aid diagnosis and identify new avenues for therapeutic intervention. We investigated how disruptions in hippocampal reactivations relate to place cell stability and spatial memory deficits in an Alzheimer's mouse model. Using the App knockin mouse model NL-G-F, we conducted simultaneous behavioral and electrophysiological recordings in a radial arm maze. NL-G-F mice exhibited significant impairments in memory performance, demonstrated by an increased propensity to revisit arms, compared with wild-type controls. These memory deficits were associated with reduced stability of hippocampal place cells, which was particularly pronounced following rest periods. Crucially, although wild-type mice showed enhanced place cell stability after quiescence, NL-G-F mice failed to exhibit this consolidation. Although the rate of hippocampal reactivation events during rest remained unchanged, analysis of replay content revealed significantly degraded replay quality in NL-G-F mice. This degradation manifested as disrupted cell recruitment and reduced co-firing structure within reactivation events, both of which predicted the failure of offline place cell stabilization. Together, these findings suggest that compromised reactivation quality may underlie disruptions in offline consolidation processes, offering a potential mechanism for memory dysfunction in Alzheimer's disease.},
}

@article {pmid41616387,
year = {2026},
author = {Upadhayay, S},
title = {Unrevealing role of TLRs/NLRP receptors in halting Alzheimer's neuroinflammation: Current progress and existing therapies.},
journal = {International immunopharmacology},
volume = {173},
number = {},
pages = {116285},
doi = {10.1016/j.intimp.2026.116285},
pmid = {41616387},
issn = {1878-1705},
abstract = {Alzheimer's disease (AD) is a multifactorial condition caused by genetic, environmental, metabolic, and immunological factors. These pathological alterations trigger oxidative stress, excitotoxicity, and neuroinflammation, leading to the degeneration of cholinergic neurons in the brain. Several studies have found that persistent neuroinflammation plays a key role in AD progression; still, no curative medicine is available to halt the disease progression. For this reason, exploring new target-based therapy is necessary for AD treatment. The current review aims to understand the inflammatory processes associated with the activation of toll-like receptors (TLRs) and Inflammasomes (NLRPs) in AD progression. Additionally, the impact of TLR and NLRP inhibitors on improving the condition of AD patients. As multiple studies have confirmed, TLR/NLRP activation stimulates the infiltration of inflammatory cytokines, which enhances AD severity. Similarly, various studies have shown that inhibition of the TLR/NLRP signaling axis reduces oxidative stress, inflammatory cytokines, and apoptosis, thereby demonstrating a neuroprotective effect. This review examines the roles of TLR and NLRP pathways in AD progression, focusing on preclinical and clinical evidence supporting the neuroprotective benefits of targeting these pathways in AD. This review extensively examined the molecular mechanisms of TLR/NLRP inhibitors, highlighting recent discoveries that could be used to initiate clinical trials in patients with Alzheimer's.},
}

@article {pmid41615932,
year = {2026},
author = {Hedaya, RJ},
title = {Iterative Dual-AI Consultation for Error Detection in Clinical Medicine: A Case Study Demonstrating Convergent Validity Through Cross-Validation of Large Language Models.},
journal = {Alternative therapies in health and medicine},
volume = {32},
number = {1},
pages = {},
pmid = {41615932},
issn = {1078-6791},
mesh = {Humans ; Female ; Middle Aged ; Magnetic Resonance Imaging ; *Artificial Intelligence ; Reproducibility of Results ; *Alzheimer Disease/diagnostic imaging/therapy ; *Neuroimaging/methods ; Brain/diagnostic imaging ; Large Language Models ; },
abstract = {BACKGROUND: Large language models have demonstrated remarkable promise in medical data analysis, but serious concerns about reliability and error propagation persist. This study reports a novel approach of using iterative consultation between two independent AI systems to analyze complex clinical neuroimaging data.

METHODS: A 63-year-old woman with a family history of Alzheimer's disease and Parkinsonism underwent brain MRI volumetry showing apparent 10-13% increases in gray matter volume following intensive multimodal interventions (Functional Medicine and HYLANE™ treatment). Despite clinical improvement, objective cognitive testing declined during the same period. Two AI systems (Claude and Perplexity) independently analyzed neuroimaging reports, cognitive testing, and clinical data over 5-7 iterative cycles, systematically challenging each other's interpretations.

RESULTS: Initial analyses diverged substantially (45-60 percentage-point difference in probability estimates). Through autonomous error detection and cross-validation, systems converged to a consensus (<10 percentage-point difference). Critical autonomous discoveries included: (1) 3.5% increase in total intracranial volume (physiologically impossible, indicating measurement artifact), (2) 11-month temporal gap between cognitive testing and MRI, and (3) literature review revealing hyperbaric oxygen therapy produces maximum 1-2% volumetric changes. Final consensus: modest real improvements (2-4%) embedded within measurement artifact (3-5%).

CONCLUSIONS: Dual-AI iterative consultation achieved autonomous error detection, literature integration, and convergent validity without requiring human identification of critical flaws. This approach may enhance reliability in complex clinical decision-making while maintaining appropriate physician oversight.

KEYWORDS: artificial intelligence, clinical decision support, neuroimaging, automated volumetry, large language models, convergent validity, error detection.},
}

Humans
Female
Middle Aged
Magnetic Resonance Imaging
*Artificial Intelligence
Reproducibility of Results
*Alzheimer Disease/diagnostic imaging/therapy
*Neuroimaging/methods
Brain/diagnostic imaging
Large Language Models

@article {pmid41615689,
year = {2026},
author = {Francis, J and Graubard, BI and Katki, H and Jackson, SS},
title = {Sex and All-Cause Mortality in the US, 1999 to 2019.},
journal = {JAMA network open},
volume = {9},
number = {1},
pages = {e2556299},
doi = {10.1001/jamanetworkopen.2025.56299},
pmid = {41615689},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; Middle Aged ; United States/epidemiology ; Adult ; Cause of Death/trends ; Prospective Studies ; Aged ; Nutrition Surveys ; *Mortality/trends ; Sex Factors ; Proportional Hazards Models ; Young Adult ; },
abstract = {IMPORTANCE: While life expectancy in the US has increased among both sexes, a significant sex gap in mortality has been consistently observed during the past 2 decades.

OBJECTIVE: To examine differences in mortality rates between males and females for overall mortality and the leading 9 causes of mortality (coded by the National Death Index as diseases of the heart, malignant neoplasms, chronic lower respiratory diseases, unintentional injuries, cerebrovascular diseases, Alzheimer disease, diabetes, influenza and pneumonia, and nephritis, nephrotic syndrome, and nephrosis).

This prospective cohort study included adults 20 years or older participating in the National Health and Nutrition Examination Survey (NHANES) cycles between 1999 and 2016. Data were linked to the National Death Index from the date of survey participation through December 31, 2019. Data were analyzed from July 16, 2024, to August 14, 2025.

EXPOSURE: Participation in the 1999-2016 NHANES cycles.

MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression was used to estimate male-to-female hazard ratios (MF HR) for overall and cause-specific mortality, adjusting for sociodemographic characteristics (eg, age, race and ethnicity), behavioral factors (eg, smoking, alcohol use), and chronic conditions (eg, diabetes, hypertension). The adjusted MF HRs were stratified by self-rated health, race and ethnicity, income, and educational level.

RESULTS: Among 47 056 participants (52.0% female and 48.0% male [weighted]), 12.9% (12.2% females and 13.6% males) were deceased at the end of follow-up. Males had a 63% higher risk of all-cause mortality compared with females, with the largest difference in mortality among individuals who died from heart disease (MF HR, 1.96; 95% CI, 1.72-2.24). The MF HR differed significantly across race and ethnicity for heart disease (range, 0.92 [95% CI, 0.36-2.35] for individuals of other race or ethnicity to 2.11 [95% CI, 1.80-2.48] for White individuals; P = .02 for interaction) and across income quartiles for mortality due to cerebrovascular diseases (range, 0.59 [95% CI, 0.25-1.38] for highest to 2.25 [95% CI, 1.31-3.86] for lowest income; P = .03 for interaction) and accidents (range, 0.57 [95% CI, 0.16-1.99] for highest income to 2.40 [95% CI, 1.03-5.58] for third highest income; P = .02 for interaction). No difference in the MF HR was found across self-rated health categories or education attainment levels. Information on covariates was largely collected by self-report, resulting in underreporting or overreporting due to social desirability bias. How these factors may have changed leading up to the time of mortality could not be accounted for.

CONCLUSIONS: In this cohort study of adult NHANES participants, after accounting for a wide range of risk factors, the sex gap in mortality remained for most causes of mortality, suggesting there may be intrinsic biological factors (eg, sex hormones, chromosomes, immune response) associated with sex differences in mortality. Further research should investigate the effects of sex-linked biological factors on mortality.},
}

Humans
Male
Female
Middle Aged
United States/epidemiology
Adult
Cause of Death/trends
Prospective Studies
Aged
Nutrition Surveys
*Mortality/trends
Sex Factors
Proportional Hazards Models
Young Adult

@article {pmid41615615,
year = {2026},
author = {Zou, P and Huang, Z and Zhang, Y and Zong, X and Zhang, Q},
title = {Myelin Lipid Reserves as a Conditional Metabolic Buffer: Implications for Alzheimer's Disease and Ischemic Stroke.},
journal = {Neuromolecular medicine},
volume = {28},
number = {1},
pages = {7},
pmid = {41615615},
issn = {1559-1174},
}

@article {pmid41615513,
year = {2026},
author = {Begum, S and De Alvarez, JA and Manzoni, C and Arber, C and Lewis, PA},
title = {In Silico Phosphoproteomic Analysis Reveals Divergent Regulation of Presenilin 1 and Presenilin 2.},
journal = {Neuromolecular medicine},
volume = {28},
number = {1},
pages = {5},
pmid = {41615513},
issn = {1559-1174},
support = {IF\R2\222002//Royal Society/ ; },
mesh = {*Presenilin-1/metabolism/genetics/chemistry ; *Presenilin-2/metabolism/genetics/chemistry ; Humans ; Phosphorylation ; Proteomics/methods ; Protein Processing, Post-Translational ; Alzheimer Disease/genetics/metabolism ; Computer Simulation ; Amyloid Precursor Protein Secretases/metabolism ; Computational Biology ; },
abstract = {The Presenilins are multi-pass transmembrane proteins that form part of the multi-protein gamma secretase complex. The hydrolytic activity of the gamma secretase complex is responsible for the cleavage of a wide range of substrates, including the amyloid precursor protein (APP) - a proteolytic event that is the final step in the production of the amyloid beta peptide, a protein fragment deposited in the brains of individuals with Alzheimer's disease (AD). Both PSEN1 and PSEN2, the genes encoding the Presenilins, are mutated in familial AD, generating intense interest in the activity and function of these proteins. Despite this attention, the post-translational modification and regulation of the Presenilins is poorly understood. In order to address this gap in our knowledge, a bioinformatic approach was taken to examine the extant evidence for Presenilin phosphorylation. Derived from the Phosphosite repository, these data reveal divergent patterns of phosphorylation across Presenilin 1 and 2, highlighting distinct regulatory pathways that have implications for our understanding of the biology of these proteins, gamma secretase, and drug discovery targeting this complex.},
}

*Presenilin-1/metabolism/genetics/chemistry
*Presenilin-2/metabolism/genetics/chemistry
Humans
Phosphorylation
Proteomics/methods
Protein Processing, Post-Translational
Alzheimer Disease/genetics/metabolism
Computer Simulation
Amyloid Precursor Protein Secretases/metabolism
Computational Biology

@article {pmid41615512,
year = {2026},
author = {Cecchini, MA and Studart-Neto, A and Moraes, NC and Carneiro, CG and Gomes, AC and Buchpiguel, CA and Brucki, SMD and Coutinho, AM and Nitrini, R and Yassuda, MS},
title = {Short-term memory conjunctive binding in subjective cognitive decline: A PET biomarker-based study.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {107},
pmid = {41615512},
issn = {1432-1459},
support = {2016/25000-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; },
mesh = {Humans ; Male ; Female ; *Positron-Emission Tomography ; Aged ; *Cognitive Dysfunction/diagnostic imaging/psychology/metabolism ; Neuropsychological Tests ; Aniline Compounds ; *Memory, Short-Term/physiology ; Middle Aged ; Biomarkers ; Thiazoles ; Fluorodeoxyglucose F18 ; Aged, 80 and over ; *Alzheimer Disease/diagnostic imaging ; *Brain/diagnostic imaging/metabolism ; },
abstract = {The Short-Term Memory Conjunctive Binding (STMCB) test assesses the ability to maintain integrated shape-colour associations in memory. It has been applied to detect Alzheimer's disease (AD) across the continuum, from preclinical stages and subjective cognitive decline (SCD) to dementia. The objective of the present study was to examine whether the STMCB test can differentiate individuals at very early stages of AD from controls. The sample included 67 participants with normal performance on standard neuropsychological tests. Participants were classified as controls or as having SCD based on self-reported memory complaints. Twenty-three controls and 44 individuals with SCD completed the STMCB test. All individuals also underwent a comprehensive neuropsychological evaluation, amyloid ([[11]C]PIB) and FDG-PET scans. No significant group differences were observed in STMCB test performance between the groups. Furthermore, the STMCB test did not distinguish between amyloid-negative controls and SCD participants with amyloid pathology. These findings suggest that binding deficits may emerge later in the AD continuum, particularly when tau deposition or neurodegeneration is present.},
}

Humans
Male
Female
*Positron-Emission Tomography
Aged
*Cognitive Dysfunction/diagnostic imaging/psychology/metabolism
Neuropsychological Tests
Aniline Compounds
*Memory, Short-Term/physiology
Middle Aged
Biomarkers
Thiazoles
Fluorodeoxyglucose F18
Aged, 80 and over
*Alzheimer Disease/diagnostic imaging
*Brain/diagnostic imaging/metabolism

@article {pmid41615392,
year = {2026},
author = {Ye, M and Pan, X},
title = {Correlation of White Matter Lesions, Cerebral Blood Flow, and Cognitive Decline in Patients With Alzheimer's Disease and Vascular Dementia.},
journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists},
volume = {41},
number = {1},
pages = {},
doi = {10.1093/arclin/acaf113},
pmid = {41615392},
issn = {1873-5843},
mesh = {Humans ; *Alzheimer Disease/complications/pathology/physiopathology/diagnostic imaging ; Aged ; Male ; Female ; *Dementia, Vascular/complications/pathology/physiopathology/diagnostic imaging ; Cross-Sectional Studies ; *Cerebrovascular Circulation/physiology ; Middle Aged ; *White Matter/pathology/diagnostic imaging ; Aged, 80 and over ; Magnetic Resonance Imaging ; *Cognitive Dysfunction/diagnostic imaging/etiology/physiopathology/pathology ; Atrophy/pathology ; Neuropsychological Tests ; *Brain/pathology ; },
abstract = {OBJECTIVE: This study investigated the relationship between white matter lesions (WMLs), cerebral blood flow (CBF), and cognitive decline in a mixed cohort of patients diagnosed with Alzheimer's disease (AD) and vascular dementia (VaD).

METHOD: This cross-sectional study included 100 patients with AD or VaD (ages 55-85) and 50 age- and education-matched healthy controls. Participants underwent neuroimaging and cognitive assessment. Volumetric WMLs were quantified using FLAIR MRI, and CBF was measured with arterial spin labeling MRI. Cognitive function was evaluated using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Structural atrophy was also visually rated, and biochemical markers were analyzed.

RESULTS: Compared to controls, the AD/VaD patient group had a significantly higher WML volume (p < .001), reduced global CBF (p < .001), greater brain atrophy, and worse ADAS-Cog scores (p < .001). A hierarchical multiple linear regression analysis in the patient group revealed that WML volume (β = 0.55, p < .001) and global CBF (β = -0.38, p < .001) were significant independent predictors of ADAS-Cog scores after controlling for age, education, and brain atrophy. Brain atrophy itself was also a significant predictor (β = 0.21, p = .005). The model explained 72% of the variance in cognitive scores.

CONCLUSIONS: In a clinically mixed dementia cohort, the burden of WMLs and the magnitude of CBF reduction are strongly associated with the severity of cognitive impairment. These findings highlight the critical contribution of cerebrovascular pathology to cognitive dysfunction and underscore the value of quantitative imaging markers in understanding dementia's neurobiological substrates.},
}

Humans
*Alzheimer Disease/complications/pathology/physiopathology/diagnostic imaging
Aged
Male
Female
*Dementia, Vascular/complications/pathology/physiopathology/diagnostic imaging
Cross-Sectional Studies
*Cerebrovascular Circulation/physiology
Middle Aged
*White Matter/pathology/diagnostic imaging
Aged, 80 and over
Magnetic Resonance Imaging
*Cognitive Dysfunction/diagnostic imaging/etiology/physiopathology/pathology
Atrophy/pathology
Neuropsychological Tests
*Brain/pathology

@article {pmid41615391,
year = {2026},
author = {Oliveri, S and Gastaldo, F and Maiorana, NV and Guidetti, M and Bocci, T and Rosci, C and Marceglia, S and Priori, A},
title = {Apathy and Depression Impact on Cognitive Decline: Neuropsychological Specificities across Neurodegenerative Diseases.},
journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists},
volume = {41},
number = {1},
pages = {},
doi = {10.1093/arclin/acaf121},
pmid = {41615391},
issn = {1873-5843},
mesh = {Humans ; *Apathy/physiology ; Male ; Female ; Aged ; *Cognitive Dysfunction/psychology/complications ; Cross-Sectional Studies ; Neuropsychological Tests ; *Depression/psychology/etiology ; Activities of Daily Living/psychology ; *Parkinson Disease/psychology/complications ; Middle Aged ; Aged, 80 and over ; *Alzheimer Disease/psychology/complications ; *Dementia, Vascular/psychology/complications ; *Neurodegenerative Diseases/complications/psychology ; },
abstract = {OBJECTIVE: Apathy is a common symptom across neurodegenerative diseases with origins still debated. "Vascular apathy hypothesis" by Van der Mast suggests vascular pathologies precede apathy. Other evidence points to dysfunction in dopamine pathways, driving apathy by impairing goal-directed behaviour. The impact of apathy on cognitive decline and autonomy, particularly with coexisting depression, remains unclear. This cross-sectional study aimed to (1) characterize apathy in vascular dementia, Parkinson's disease (PD), and Mild Cognitive Impairment-Alzheimer Disease (MCI-AD) regarding incidence, severity, and cognitive specificity; (2) differentiate effects of apathy and depression on cognitive impairment and daily autonomy (Activities of Daily Living [ADL]).

METHOD: Fifty-three patients underwent neuropsychological testing and completed the Geriatric Depression Scale, Starkstein's Apathy Scale, and ADL questionnaire at a clinical neuropsychology outpatient setting in Milan.

RESULTS: 56% patients had cardiovascular pathologies, 20% had PD, and 22% had MCI-AD. Neither prevalence nor severity of apathy or depression differed significantly across diseases. Hierarchical regression showed apathy predicted language initiative controlling for depression (R2 = 0.249; F(2) = 4.144; p = .028), and inversely correlated with working memory, language and frontal functioning, while depression predicted autonomy controlling for apathy (R2 = 0.234; F (2) = 3.821; p = .036).

CONCLUSIONS: Apathy is prevalent across different neurodegenerative diseases and exacerbates specific cognitive impairments. Distinguishing vascular apathy from other forms remains challenging.},
}

Humans
*Apathy/physiology
Male
Female
Aged
*Cognitive Dysfunction/psychology/complications
Cross-Sectional Studies
Neuropsychological Tests
*Depression/psychology/etiology
Activities of Daily Living/psychology
*Parkinson Disease/psychology/complications
Middle Aged
Aged, 80 and over
*Alzheimer Disease/psychology/complications
*Dementia, Vascular/psychology/complications
*Neurodegenerative Diseases/complications/psychology

@article {pmid41614917,
year = {2026},
author = {Zhan, M and Chen, H and Fu, X and Tang, S and Song, X and Li, H and Zhu, L and Wang, B},
title = {TUDCA Ameliorates Cognitive Impairment in APP/PS1 Mice by Modulating the Microbiota-Gut-Brain Axis.},
journal = {Current issues in molecular biology},
volume = {48},
number = {1},
pages = {},
doi = {10.3390/cimb48010087},
pmid = {41614917},
issn = {1467-3045},
support = {2020ZY013802//Chongqing Municipal Health Commission and Chongqing Science and Technology Bureau/ ; },
abstract = {Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer's disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP/PS1 mice. Behavioral tests, assessments of amyloid-β (Aβ) deposition, neuroinflammation, peripheral inflammatory responses, intestinal barrier integrity, and gut microbiota composition were performed, along with pseudo-sterile mouse experiments and fecal microbiota transplantation (FMT). The expression of genes related to the TLR4/NF-κB/NLRP3 pathway was also examined. TUDCA significantly ameliorated cognitive impairments, reduced Aβ accumulation, and suppressed inflammatory responses in both the central nervous system and peripheral tissues. It improved intestinal barrier function and reshaped gut microbial composition by reducing pro-inflammatory taxa. FMT demonstrated that TUDCA-modulated microbiota contributed to improved learning and memory in AD mice, whereas antibiotic-induced pseudo-sterility indicated that TUDCA also exerted cognitive benefits independent of gut flora. Moreover, TUDCA inhibited the activation of the TLR4/NF-κB/NLRP3 pathway. In conclusion, TUDCA alleviates AD-related cognitive deficits partly through modulation of the microbiota-gut-brain axis while also acting via microbiota-independent mechanisms, supporting its potential as a promising therapeutic strategy for AD.},
}

@article {pmid41614916,
year = {2026},
author = {Zhao, X and Yin, J and Du, B and Fan, W and Chen, Y and Yang, Y and Fang, F and Guan, J},
title = {Behavioral, Histopathological, and Biochemical Implications of Aloe Emodin in Copper-Aβ-Induced Alzheimer's Disease-like Model Rats.},
journal = {Current issues in molecular biology},
volume = {48},
number = {1},
pages = {},
doi = {10.3390/cimb48010086},
pmid = {41614916},
issn = {1467-3045},
support = {82074001//National Natural Science Foundation of China/ ; zyyzdxk-2023265//the State Administration of Traditional Chinese Medicine High-level TCM key discipline Con-struction Project/ ; },
abstract = {Simultaneously inhibiting beta-amyloid protein (Aβ) aggregation and reducing metal ion overload in the brain is a promising strategy for treating Alzheimer's disease (AD). Aloe emodin (AE) is one of the major components of the traditional Chinese medicine rhubarb. Based on its reported pharmacological effects and its structural affinity for metal ions, this study aims to explore the potential of AE in improving AD pathology. Through the injection of Aβ or copper-Aβ complex in the bilateral hippocampus of rats, we constructed two kinds of nontransgenic animal models. Behavioral tests were used to evaluate cognitive impairment, and the effects of AE on neuronal damage and Aβ deposition were measured via Nissl staining and immunohistochemistry. Furthermore, we detected copper content in the serum and brain tissues as well as some biochemical indexes of Aβ cascade pathology in the brain tissues of model rats to explore the mechanism of action. AE treatment decreased copper accumulation and regulated Aβ metabolism in the brain of model rats, thereby improving Aβ deposition, memory impairment, hippocampal nerve cell damage, and related biochemical indicators. AE ameliorated the AD pathology of the model rats by targeting copper-induced Aβ toxicity, revealing a mechanism of action by which AE may exhibit good clinical efficacy in treating AD.},
}

@article {pmid41614805,
year = {2025},
author = {Alhadrami, M and Stone, G and Barker, RM and Palmer, JC and Kehoe, PG and Perks, CM},
title = {Androgen Effects on Amyloid Precursor Protein Processing Pathways in Cancer: A Systematic Review.},
journal = {Current issues in molecular biology},
volume = {47},
number = {12},
pages = {},
doi = {10.3390/cimb47121041},
pmid = {41614805},
issn = {1467-3045},
support = {TLD-CAF22-009/PCUK_/Prostate Cancer UK/United Kingdom ; na//Saudi Arabia Cultural Bureau./ ; na//Sigmund Gestetner Foundation/ ; na//Bristol Urology Institute/ ; },
abstract = {Androgens have been shown to be linked to cancer progression, particularly in hormone-dependent cancers such as prostate and breast cancer, but also other cancers. Amyloid precursor protein (APP), which has primarily been studied in Alzheimer's disease, is gaining recognition for its role in tumor growth and survival. While APP overexpression and androgen receptor (AR) signaling are each associated with cancer progression, the connection between androgens and APP processing in cancer has not been thoroughly investigated. This systematic review was conducted through a comprehensive search of PubMed, Scopus, Web of Science, and EMBASE between 2000 to 2024 for studies examining the effects of androgens on APP and its cleavage enzymes in cancer. Five experimental studies met the inclusion criteria, covering prostate and breast cancer models. Data were extracted and synthesized narratively due to heterogeneity in methods and outcomes. Three studies reported that dihydrotestosterone (DHT) or AR agonists increased the expression and nuclear translocation of ADAM10, a key α-secretase enzyme in the non-amyloidogenic APP processing pathway. Two studies identified APP as an androgen-responsive gene, showing that androgens upregulated APP expression in prostate and breast cancer cells and promoted the proliferation of cancer cells. Inhibition or knockdown of APP and ADAM10 reduced proliferation, supporting their roles in tumor progression. Androgen signaling modulates APP processing in cancer, particularly through the non-amyloidogenic pathway; however, significant knowledge gaps remain. Further studies are needed to explore the interaction between androgens and APP processing in other cancer types, as well as to elucidate downstream signaling pathways regulated at the gene expression level.},
}

@article {pmid41614741,
year = {2025},
author = {Alharbi, LI and Badr, E and Donia, A and Monir, E},
title = {Comparative Multi-Omics Analysis Identifies Shared Transcriptomic Signatures and Therapeutic Targets in Alzheimer's, Parkinson's, and Huntington's Diseases.},
journal = {Current issues in molecular biology},
volume = {47},
number = {12},
pages = {},
doi = {10.3390/cimb47120976},
pmid = {41614741},
issn = {1467-3045},
abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are major neurodegenerative disorders that share certain pathological features but differ in their genetic etiology and clinical presentation. Their potential molecular intersections remain incompletely understood. In this research, we conducted a comparative transcriptomic analysis using postmortem brain RNA-seq datasets from AD (GSE53697), PD (GSE68719), and HD (GSE64810) to identify shared and disease-specific transcriptional signatures. Differentially expressed genes (DEGs) were determined and functionally characterized through Gene Ontology (GO) enrichment. Protein-protein interaction (PPI) networks were generated using STRING and visualized in Cytoscape to identify central hub genes, followed by gene-disease and drug-interaction analyses to assess functional and therapeutic relevance. Ten DEGs were found to overlap among the three disorders, exhibiting variable directions of regulation across diseases. Enrichment analysis indicated convergence on immune- and inflammation-related biological processes. Key hub genes, including MMP9, LCN2, CXCL2, CCL2, S100A8, and S100A9, were identified as central nodes within the PPI network. Although the overlap in DEGs was limited, the findings suggest that neuroinflammatory signaling represents a shared molecular theme across AD, PD, and HD, warranting further validation in independent cohorts.},
}

@article {pmid41614697,
year = {2026},
author = {Liu, G and Xu, M},
title = {Improving cognitive function and functional independence in Alzheimer's disease: the role of specialized dementia nursing.},
journal = {Neurological research},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/01616412.2026.2622477},
pmid = {41614697},
issn = {1743-1328},
abstract = {OBJECTIVE: This study evaluated the impact of a specialized dementia nursing program on cognitive function, self-care ability, psychological status, and quality of life in patients with Alzheimer's disease (AD).

METHODS: Data from 131 AD patients admitted to our hospital between January 2019 and August 2021 were analyzed. Based on the nursing method, the patients were divided into a control group that received routine nursing care (n = 58) and an intervention group that implemented routine nursing care combined with specialized nursing (n = 73). Psychological status, daily living and self-care ability, cognitive function, quality of life, and nursing satisfaction were compared between the two groups.

RESULTS: After specialized nursing, the intervention group showed significantly greater reductions in HAMA and HAMD scores and greater increases in CD - RISC, ADL, and ESCA scores compared with the control group (p < 0.05). The intervention group also had higher MMSE, ADCS - ADL, and DQOL scores and lower ADAS - Cog scores compared to the control group (p < 0.05). Nursing satisfaction was also higher in the intervention group than in the control group (p < 0.05).

CONCLUSION: Specialized dementia nursing can enhance cognitive function, self-care ability, psychological resilience, and quality of life in AD patients, and increases satisfaction with nursing care.},
}

@article {pmid41614577,
year = {2026},
author = {Ma, P and Cui, H and Ren, L and Liu, Y and Cen, M},
title = {miR-769-5p as a Novel Biomarker and Functional Mediator in Alzheimer's Disease: Targeting CREB5 to Alleviate Oxidative Injury.},
journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica},
volume = {134},
number = {2},
pages = {e70148},
doi = {10.1111/apm.70148},
pmid = {41614577},
issn = {1600-0463},
support = {LHGJ20210499//Research Project on the mechanism of Linc RCAD regulating CDH4 to promote multipotent glioblastoma invasion/ ; },
mesh = {Humans ; *MicroRNAs/blood/genetics/metabolism ; *Alzheimer Disease/diagnosis/genetics/metabolism/pathology/blood ; *Oxidative Stress ; *Biomarkers/blood ; *Cyclic AMP Response Element-Binding Protein/genetics/metabolism/blood ; Female ; Male ; Aged ; Cognitive Dysfunction/diagnosis/genetics ; Amyloid beta-Peptides/metabolism ; Aged, 80 and over ; Middle Aged ; Cell Proliferation ; Cell Line, Tumor ; Cyclic AMP Response Element-Binding Protein A ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with mild cognitive impairment (MCI) as its critical prodromal stage. Identifying reliable biomarkers to distinguish AD from MCI is key for early intervention. This study explored miR-769-5p's potential as a diagnostic biomarker for AD and its mechanism, especially its links to oxidative stress and target gene CREB5. Serum miR-769-5p and CREB5 levels were measured via qRT-PCR. Cellular models used Aβ42-treated SH-SY5Y cells, validated by confirming key AD pathologies including increased Tau phosphorylation. Functional/mechanistic assessments employed CCK-8, MDA, SOD, and dual-luciferase reporter assays. Clinically, multivariate logistic regression identified miR-769-5p as a strong independent protective factor (OR = 0.029, p < 0.001). miR-769-5p was downregulated in AD versus MCI and accurately distinguished them (AUC = 0.919). In Aβ-treated cells, miR-769-5p overexpression reduced Aβ-induced proliferation suppression and oxidative stress (lower MDA, higher SOD, all p < 0.01), while inhibition worsened damage. CREB5, a direct miR-769-5p target, was upregulated in AD. Functionally, rescue assays confirmed CREB5 overexpression reversed miR-769-5p mimic's protection. In conclusion, serum miR-769-5p is a promising biomarker for AD-MCI distinction and may protect against AD by targeting CREB5 to mitigate oxidative stress.},
}

Humans
*MicroRNAs/blood/genetics/metabolism
*Alzheimer Disease/diagnosis/genetics/metabolism/pathology/blood
*Oxidative Stress
*Biomarkers/blood
*Cyclic AMP Response Element-Binding Protein/genetics/metabolism/blood
Female
Male
Aged
Cognitive Dysfunction/diagnosis/genetics
Amyloid beta-Peptides/metabolism
Aged, 80 and over
Middle Aged
Cell Proliferation
Cell Line, Tumor
Cyclic AMP Response Element-Binding Protein A

@article {pmid41614554,
year = {2026},
author = {Büyükgök, D and Ince Guliyev, E and Bilgiç, B},
title = {Apathy in dementia: pharmacological and nonpharmacological treatment strategies.},
journal = {Current opinion in psychiatry},
volume = {39},
number = {2},
pages = {160-167},
doi = {10.1097/YCO.0000000000001054},
pmid = {41614554},
issn = {1473-6578},
mesh = {Humans ; *Apathy/drug effects ; *Dementia/therapy/drug therapy/psychology ; Methylphenidate/therapeutic use ; Alzheimer Disease/therapy/psychology ; Central Nervous System Stimulants/therapeutic use ; Cholinesterase Inhibitors/therapeutic use ; },
abstract = {PURPOSE OF REVIEW: Apathy is one of the most prevalent and disabling symptoms of neurodegenerative disorders, yet targeted treatments remain poorly defined. In recent years, growing interest in its conceptualization and management has led to an increasing number of randomized controlled trials (RCTs) and meta-analyses addressing both pharmacological and nonpharmacological interventions.

RECENT FINDINGS: Among pharmacological approaches, methylphenidate presented with early reductions in apathy with an acceptable safety profile in multiple RCTs, including a large 6-month trial. However, the sustainability of effect has not been fully achieved. Other stimulants, bupropion, and conventional Alzheimer's medications such as cholinesterase inhibitors and memantine show inconsistent or limited effects. Antidepressants and antipsychotics are not recommended for apathy, although selected agents may benefit comorbid conditions. As for the nonpharmacological interventions, evidence supports the benefits of physical exercise and the emerging promise of neuromodulation. Technology-based interventions are feasible but show variable efficacy.

SUMMARY: Methylphenidate currently represents the most studied pharmacological agent for apathy in Alzheimer's disease (AD). However, optimal management is likely to combine pharmacological and psychosocial strategies tailored to the patient context. Future studies should include pragmatic trials with apathy as a primary endpoint, long-term follow-up, and expansion beyond AD.},
}

Humans
*Apathy/drug effects
*Dementia/therapy/drug therapy/psychology
Methylphenidate/therapeutic use
Alzheimer Disease/therapy/psychology
Central Nervous System Stimulants/therapeutic use
Cholinesterase Inhibitors/therapeutic use

@article {pmid41614494,
year = {2026},
author = {Theodorou, A and Melanis, K and Athanasaki, A and Palaiodimou, L and Stefanou, MI and Tsalouchidou, PE and Vassilopoulos, E and Kouzoupis, A and Themistocleous, M and Paraskevas, GP and Tzavellas, E},
title = {Cerebral amyloid angiopathy and amyloid load distribution detected on amyloid-positron emission tomography: A systematic review and meta-analysis.},
journal = {European stroke journal},
volume = {11},
number = {1},
pages = {},
doi = {10.1093/esj/23969873251349657},
pmid = {41614494},
issn = {2396-9881},
mesh = {Humans ; *Cerebral Amyloid Angiopathy/diagnostic imaging/metabolism ; *Positron-Emission Tomography/methods ; *Alzheimer Disease/diagnostic imaging/metabolism ; *Amyloid/metabolism ; Aged ; Female ; Male ; Hypertension/complications/diagnostic imaging ; *Brain/diagnostic imaging/metabolism ; },
abstract = {INTRODUCTION: There are limited data regarding the amyloid positron emission tomography (PET) imaging among patients with Cerebral Amyloid Angiopathy (CAA). We sought to assess the amyloid load distribution detected on amyloid-PET among CAA patients compared to patients with Alzheimer's Disease (AD), patients with hypertension (HTN) related hemorrhage (ICH) and healthy controls (HC).

PATIENTS AND METHODS: A systematic review and meta-analysis of published studies with available data on global and regional amyloid-PET uptake was conducted. Comparisons with respect to amyloid load distribution were investigated using random-effects models based on the ratio of mean (RoM) amyloid-PET uptake. RoM < 1 and RoM > 1 indicate lower and higher global or regional amyloid-PET uptake in CAA compared to another population, respectively.

RESULTS: We identified 16 cohorts, comprising 271 CAA patients (mean age: 72 years; women: 46%) versus 130 AD patients (mean age: 73 years; women: 44%), 180 patients with HTN-related ICH (mean age: 66 years; women: 36%) and 61 HC (mean age: 71 years; women: 46%) with available data on amyloid-PET. Global amyloid PET ratio differentiated CAA from AD [RoM: 0.93; 95% CI: 0.90-0.96; p < 0.0001], HTN-related ICH [RoM: 1.25; 95% CI: 1.20-1.31; p < 0.0001], and HC [RoM: 1.26; 95% CI: 1.23-1.29; p < 0.0001]. Occipital amyloid-PET uptake [RoM: 1.20; 95% CI: 1.15-1.26; p < 0.0001] was higher in CAA compared to HTN-related ICH, and Occipital-to-global [RoM: 1.05; 95% CI: 1.03-1.07; p < 0.0001] ratio of amyloid-PET uptake differentiated also CAA from AD.

CONCLUSIONS: CAA is characterized by a distinct amyloid-PET burden and distribution compared to AD patients, patients with HTN-related ICH and HC. These findings may contribute to the design and conduct of future randomized controlled clinical trials, aiming to treat CAA at preclinical stages.},
}

Humans
*Cerebral Amyloid Angiopathy/diagnostic imaging/metabolism
*Positron-Emission Tomography/methods
*Alzheimer Disease/diagnostic imaging/metabolism
*Amyloid/metabolism
Aged
Female
Male
Hypertension/complications/diagnostic imaging
*Brain/diagnostic imaging/metabolism

@article {pmid41614286,
year = {2026},
author = {Hammers, DB and Eloyan, A and Thangarajah, M and Taurone, A and Gao, S and Beckett, L and Kirby, K and Dage, JL and Nudelman, K and Aisen, P and Reman, R and Vemuri, P and La Joie, R and Touroutoglou, A and Atri, A and Clark, D and Day, GS and Duara, R and Graff-Radford, NR and Honig, LS and Jones, DT and Masdeu, JC and Mendez, MF and Womack, K and Musiek, E and Onyike, CU and Riddle, M and Grant, I and Rogalski, E and Johnson, ECB and Salloway, S and Sha, SJ and Turner, RS and Wingo, TS and Wolk, DA and Carrillo, MC and Dickerson, BC and Rabinovici, GD and Apostolova, LG and , and , },
title = {Relationship between age and severity of cognitive impairment at diagnosis for early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71160},
doi = {10.1002/alz.71160},
pmid = {41614286},
issn = {1552-5279},
support = {/NH/NIH HHS/United States ; /AG/NIA NIH HHS/United States ; /EB/NIBIB NIH HHS/United States ; /CAPMC/CIHR/Canada ; //Northern California Institute for Research and Education/ ; LDRFP-21-818464/ALZ/Alzheimer's Association/United States ; },
mesh = {Humans ; *Alzheimer Disease/diagnosis/complications/psychology ; Male ; Female ; Aged ; *Cognitive Dysfunction/diagnosis ; Neuropsychological Tests ; Age of Onset ; Severity of Illness Index ; Middle Aged ; Aged, 80 and over ; Executive Function ; Age Factors ; },
abstract = {INTRODUCTION: Recent work has identified unique cognitive profiles for early-onset Alzheimer's disease (EOAD) relative to late-onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions.

METHODS: A series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein ε4 status.

RESULTS: Significant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non-amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD.

DISCUSSION: In the age of disease-modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65.

HIGHLIGHTS: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same-aged peers across most domains. Both groups displayed positive relationships between impairment among non-amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.},
}

Humans
*Alzheimer Disease/diagnosis/complications/psychology
Male
Female
Aged
*Cognitive Dysfunction/diagnosis
Neuropsychological Tests
Age of Onset
Severity of Illness Index
Middle Aged
Aged, 80 and over
Executive Function
Age Factors

@article {pmid41614050,
year = {2026},
author = {Scheijbeler, EP and Molleson, M and Schoonhoven, DN and van Nifterick, AM and Hillebrand, A and de Haan, W and Stam, CJ and Gouw, AA},
title = {Replication and validation of two novel magnetoencephalography functional connectivity measures in Alzheimer's disease.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
pmid = {41614050},
issn = {2837-6056},
abstract = {Two novel magnetoencephalography (MEG) functional connectivity measures were recently shown to be superior to well-known measures of amplitude correlation and phase synchronization in detecting early stage neurophysiological abnormalities, particularly neuronal hyperexcitability, in a computational model of Alzheimer's disease (AD). The reliability of these measures in empirical data remains to be evaluated. We investigated whether the Phase Lag Time (PLT) and Joint Permutation Entropy (JPE) could identify consistent patterns of between- and within-group functional connectivity in the theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) frequency bands in eyes-closed resting-state MEG recordings from two independent cohorts of AD patients (n = 28/n = 29) and control subjects (n = 29/n = 27). We assessed the classification performance of the measures and examined their construct validity using a computational approach. Results were compared with those obtained using two previously validated functional connectivity measures, the leakage-corrected Amplitude Envelope Correlation (AEC-c) and Phase Lag Index (PLI). In both cohorts, whole-brain analysis identified significant group differences (AD patients versus control subjects) in functional connectivity estimated by PLT and JPE across the theta and beta bands (effect sizes: 0.15-0.40; p < .05). Regional analysis revealed that 43-77 regions (out of 80) showed significant group differences in these frequency bands, with significant cross-cohort correlations between regional difference scores of rp = 0.37-0.55, p < .001. PLT and JPE connectivity matrices revealed strong within-group consistency across cohorts for both AD patients and control subjects in all frequency bands (rs > 0.80, p < .001). Logistic regression models trained on whole-brain PLT or JPE values in the theta or beta band achieved area under the curve values between 0.72 and 0.78. Finally, the PLT and JPE were shown to be sensitive to changes in coupling strength in a whole-brain computational model. Across all analyses, the PLT and JPE performed as well as, or better than, the AEC-c and PLI. The PLT and JPE can reliably detect neurophysiological abnormalities related to AD from eyes-closed resting-state MEG recordings. Since accumulating evidence identifies neuronal hyperexcitability as a key pathological process in early AD and a potential therapeutic target, these novel functional connectivity measures could play a valuable role in early disease detection and the evaluation of treatments aimed at restoring the excitation-inhibition balance in AD.},
}

@article {pmid41614007,
year = {2026},
author = {Sharma, G and Pahnke, J and Roth, B},
title = {Polarimetric analysis of the Alzheimer's pathology in excised mouse brain tissue.},
journal = {Journal of biomedical optics},
volume = {31},
number = {1},
pages = {015002},
pmid = {41614007},
issn = {1560-2281},
mesh = {*Alzheimer Disease/pathology ; Animals ; Mice ; *Brain/pathology/diagnostic imaging ; Amyloid beta-Peptides/metabolism ; Mice, Inbred C57BL ; Plaque, Amyloid/pathology ; },
abstract = {SIGNIFICANCE: Given the rapidly ageing global population and the projected rise in dementia cases, research into Alzheimer's disease (AD) has become an urgent scientific and medical priority. Continued investigation into the molecular mechanisms and early detection of AD is therefore essential to mitigate its growing personal and societal impact. Most current AD therapies in advanced phases of development target amyloid β -peptide (A β) production, aggregation, or accumulation.

AIM: Mueller Matrix Polarimetry (MMP) has evolved into a prominent research subject, with a focus on identifying microstructural changes in biotissues. This is done by investigating light properties, which is especially useful in the early detection of brain cell degradation, among others. We set up and employed experimental MMP at three illuminating laser wavelengths (i.e., 445, 532, and 632 nm).

APPROACH: We investigated the application of MMP to mouse brain tissue containing A β plaques. The investigated samples on glass slides consisted of paraffin-embedded brain and paraffin-embedded tissue slices. The tissues were taken at various stages of ageing, i.e., 75, 100, 125, 150, 175, 200, and 225 days. Paraffin tissue blocks were used as an additional sample set for comparison.

RESULTS: We performed a comparative analysis based on the Mueller matrix elements for each age category and highlighted the importance of certain elements, e.g., m 44 , for further analysis. We also compared the trends of decomposition parameters and could correlate them with the ageing. Contrary to previous studies, we also report on retardation, diattenuation, and polarizance changes for later AD changes.

CONCLUSIONS: From the higher-order statistics, we concluded that the mean and standard deviation remained constant across the ages. Skewness values were positive and increased as the age progressed, whereas kurtosis decreased with age. The large available dataset opens the possibility of implementing machine learning methods to assist clinical diagnosis in the future.},
}

*Alzheimer Disease/pathology
Animals
Mice
*Brain/pathology/diagnostic imaging
Amyloid beta-Peptides/metabolism
Mice, Inbred C57BL
Plaque, Amyloid/pathology

@article {pmid41613887,
year = {2025},
author = {Zlobina, VV and Mitkevich, VA and Bershatsky, YV and Volynsky, PE and Pavlov, KV and Karbyshev, MS and Okhrimenko, IS and Kozin, SA and Efremov, RG and Makarov, AA and Bocharov, EV},
title = {Transient cholesterol interactions with the amyloid precursor protein involved in Alzheimer's disease pathogenesis.},
journal = {Biophysical reviews},
volume = {17},
number = {5},
pages = {1187-1198},
pmid = {41613887},
issn = {1867-2450},
abstract = {Alzheimer's disease (AD) is the most prevalent form of age-related dementia. A pathological hallmark of AD is the accumulation in the brain of amyloid-β (Aβ) peptides, which aggregate at neuronal contact points into ordered fibrils and cords, ultimately shaping into senile plaques. Various Aβ isoforms are present in healthy human brains across all age groups, where they appear to participate in neuronal signaling pathways and exhibit neuroprotective properties at normal physiological concentrations. Aβ peptides are products of stepwise proteolytic degradation of the amyloid precursor protein (APP), a membrane-bound single-span glycoprotein, by β- and γ-secretases. The APP gene contains numerous familial mutations connected to early-onset AD, most of them occurring in the transmembrane and juxtamembrane regions. The proteolytic processing of APP into Aβ is controlled by several factors, including its subcellular localization, membrane lipid composition, and potentially its association with cholesterol- and sphingolipid-enriched lipid rafts. Interestingly, structurally and functionally resembling type I membrane receptors, APP has been suggested to play a role in cholesterol sensing in the neuronal membrane rafts. By this means, APP might engage in cell signaling processes, support iron equilibrium in neurons, participate in inflammatory responses, and modulate synaptic plasticity. This concise review summarizes key findings from biophysical and structural studies investigating the interactions of APP and its proteolytic fragments with plasma membrane components, particularly cholesterol and its derivatives. These interactions are viewed in the context of both normal physiological development and AD pathogenesis.},
}

@article {pmid41613824,
year = {2026},
author = {Zawar, I and Lisgaras, CP and Sen, A and Jensen, FE and Reyes, A},
title = {Epilepsy in the Aging Brain: Time to Rethink the Narrative.},
journal = {Epilepsy currents},
volume = {},
number = {},
pages = {15357597261417707},
pmid = {41613824},
issn = {1535-7597},
abstract = {This article reflects key themes and discussions from the American Epilepsy Society Annual Meeting 2025, Epilepsy and Aging Special Interest Group (SIG) session entitled "Multimodal Biomarkers of Epilepsy in Older Adults." The perspectives presented here are intended to highlight emerging priorities for the field. Epilepsy in older adults is the fastest-growing segment of the epilepsy population worldwide. Despite rising incidence, prevalence, and substantial morbidity, care for late-onset epilepsy (LOE) remains anchored to a seizure-centric framework that inadequately addresses the broader consequences of seizures in later life. Older adults with LOE face markedly increased risks of dementia, mortality, and stroke, yet are frequently excluded from epilepsy and Alzheimer's disease (AD) clinical trials. Patient-centered outcomes, including cognition, sleep, function, and quality of life, remain underprioritized. In this article, we argue that LOE requires multimodal biomarkers and multidisciplinary care. We contend that LOE should be reframed as a biologically meaningful warning signal of network vulnerability and overlapping brain pathology, rather than a late-life complication to be managed pragmatically. Cognitive dysfunction is common, heterogeneous, and often precedes overt neurodegenerative diagnoses, positioning cognition as an early clinical signal. Neuroimaging and electrophysiological evidence further place LOE along a continuum intersecting cardiovascular risk factors, sleep disruption, and AD biology, challenging traditional silos between epilepsy and dementia care. We argue for greater inclusion of older adults in antiseizure medication trials and for the inclusion of individuals with epilepsy in AD clinical trials. We propose a brain-health-centered framework for LOE that integrates longitudinal electroencephalography, particularly sleep-inclusive strategies, routine cognitive screening with targeted neuropsychological assessment, neuroimaging, vascular and sleep risk evaluation, and selective use of neurodegenerative biomarkers when clinically actionable. Together, these shifts move care beyond seizure counting toward a comprehensive brain-health model aligned with the realities of aging epilepsy.},
}

@article {pmid41613767,
year = {2025},
author = {Lakshmanan, SK and Muthusamy, M and Dhanaraj, RK and Sureshkumar, A and Sayeed, MS and Mohamed, MYN and Rathinam, G},
title = {Effective deep convolutional neural network with attention mechanism for Alzheimer disease classification.},
journal = {Frontiers in radiology},
volume = {5},
number = {},
pages = {1698760},
pmid = {41613767},
issn = {2673-8740},
abstract = {INTRODUCTION: The reports from the Health Organizations indicates a sudden growth in neurocognitive disorders among middle-aged and elderly individuals. The accurate detection of Alzheimer's disease (AD) is essential for improving patient care, specifically during the early stages, where timely risk identification enables individuals to adopt preventive measures before irreversible brain damage occurs. Though, several studies have discovered about computerized approaches for AD, many existing techniques remain limited by inherent methodological constraints and insufficient clinical scrutiny. The current systems struggle to reliably predict the disorder in its initial stages. To reduce the need for frequent clinical visit and lower diagnostic costs, the machine learning and deep learning have emerged as powerful tools for AD detection.

METHODS: This work reviews several research relevant on studies on AD and highlights how these computational techniques can support researchers in achieving more efficient and accurate early-stage detection. The Deep Convolutional Neural Network (Deep-CNN) with Attention mechanism is proposed to augment the spatial attention module and multi-class classification of Alzheimer disease stages. The model has trained and evaluated on the OASIS dataset using subject-level which satisfy statistical-validation and standard preprocessing.

RESULTS: The proposed Deep-CNN and attention model focuses the model capacity on diagnostically relevant regions. The proposed model achieved an accuracy of 97%, which is higher than existing methods like SVM with kernels (90.5%), SVM Gaussian radial basis kernel (85%), and traditional CNN (93.5%).

DISCUSSION: The visualizations of attention mechanism are used to increase the interpretability and demonstrate the attention maps which are align with known AD biomarkers. These results indicates that the attention-guided deep models can both improve multi-class MRI classification accuracy and provide clinically useful regional explanations.},
}

@article {pmid41613766,
year = {2026},
author = {McMackin, R and Price, S and Slator, GR and Hardiman, O and Kelly, JA},
title = {JAK4D, a first-in-class thyrotropin-releasing hormone analogue, reverses scopolamine-induced memory deficits.},
journal = {Brain communications},
volume = {8},
number = {1},
pages = {fcag006},
pmid = {41613766},
issn = {2632-1297},
abstract = {There is a pressing unmet clinical and health economic need for effective drugs to treat cognitive impairment that occurs in neurodegenerative diseases. JAK4D is a first-in-class thyrotropin releasing hormone (TRH) analogue that overcomes the pharmacological limitations of thyrotropin releasing hormone and enables delivery of the long-recognized multifactorial neurotherapeutic actions of thyrotropin releasing hormone without inducing endocrine side effects. JAK4D is demonstrated to be neuroprotective and significantly reduce excitotoxic-induced hippocampal-dependent memory deficits in rat. In the present study, we used the scopolamine challenge test coupled with the novel object recognition test to evaluate the effect of JAK4D on scopolamine-induced recognition memory deficits in the male, Lister-Hooded rat. Scopolamine administration has been shown by others to mimic cholinergic and brain network disruption in neurodegenerative diseases. Although the scopolamine challenge test does not fully replicate the pathophysiology of neurodegenerative disease, such as Alzheimer's disease, it is a well-recognized acute pharmacological model for assessing the ability of pharmacological interventions to counteract memory deficits relevant to neurodegenerative diseases. In this model of cholinergic dysfunction, we also assessed the effects of thyrotropin releasing hormone, taltirelin (a degradation-stabilized thyrotropin releasing hormone analogue) and the acetylcholinesterase inhibitor, donepezil, as a positive reference compound. The discrimination (d2) index was used as the primary measure to assess the effect of treatment on scopolamine-induced performance deficit in the novel object recognition test. d2 is a standard well-recognized measure of discrimination between a novel and familiar object in the novel object recognition test, which advantageously takes into account individual differences in exploration levels. Across all investigations, JAK4D (1 mg/kg i.p.) significantly reversed scopolamine-induced recognition memory impairment (P = 0.0274, P = 0.0002, P < 0.0001). The degree of reversal of scopolamine-induced memory deficits by JAK4D (1 mg/kg i.p.) was indistinguishable from that observed for donepezil (0.1 mg/kg p.o.) (P = 0.026). Subcutaneously administered JAK4D (0.3-10.0 mg/kg) also significantly reversed this deficit (P = 0.0432-0.0021). Furthermore, similar pro-cognitive effects were exerted by thyrotropin releasing hormone (5 mg/kg i.p., P = 0.0055) and taltirelin (10 mg/kg p.o., P = 0.0002). Together, these results underscore the relevance of the central thyrotropin releasing hormone signalling system for the treatment of memory impairment. Data from the current study provide further evidence in support of the potential of JAK4D as a novel therapeutic for cognitive deficits in neurodegenerative diseases.},
}

@article {pmid41613657,
year = {2025},
author = {Arai, H and Yamamoto, H and Akiba, Y and Aiba, S and Arai, R},
title = {Amyloid Positron Emission Tomography Imaging at the Onset of Amyloid-Related Abnormalities With Edema in an Alzheimer's Disease Patient.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100276},
pmid = {41613657},
issn = {2168-8184},
abstract = {Amyloid-related imaging abnormalities with edema (ARIA-E) are known adverse events of anti-amyloid monoclonal antibody therapy for Alzheimer's disease (AD), but to our knowledge, amyloid positron emission tomography (PET) captured exactly at the moment of ARIA-E onset has not previously been reported. We report an 85-year-old woman with AD who received anti-amyloid antibody therapy for approximately one year. As part of routine post-treatment evaluation, a second amyloid PET scan obtained 16 days after her final infusion unexpectedly revealed asymptomatic ARIA-E when followed immediately by magnetic resonance imaging (MRI). Compared with the baseline, the follow-up PET showed a marked overall reduction in cortical amyloid burden, including near-complete loss of tracer uptake in the region corresponding to ARIA-E, while the adjacent white matter exhibited reduced, non-specific uptake likely related to edema. This unique, same-day PET-MRI pairing at the moment of ARIA-E detection highlights dynamic regional changes in amyloid signal during treatment and emphasizes the value of continued neuroimaging surveillance even in asymptomatic patients.},
}

@article {pmid41613637,
year = {2026},
author = {Chopra, NK and Mehta, V and Nagu, P},
title = {Unraveling the neuroprotective potential of Aegle marmelos in Alzheimer's disease: a network pharmacology and molecular docking approach.},
journal = {In silico pharmacology},
volume = {14},
number = {1},
pages = {50},
pmid = {41613637},
issn = {2193-9616},
abstract = {UNLABELLED: Alzheimer's disease (AD) is a multifaceted neurological condition noticeable by neurodegeneration, progressive cognitive impairment, and memory loss. Several interconnected pathological pathways work in harmony to present clinical AD. Currently available anti-AD therapeutics are capable of targeting a few pathways while others remain unchecked, leading to AD progression despite continuous therapy. The current study aimed to discover the potential of Aegle marmelos (AM) bioactives against AD and identify key pathological targets using Network Pharmacology (NP) and Molecular Docking approach. 14 bioactive compounds from AM were identified to have potential anti-AD activity based on favorable pharmacokinetic, safety profiles, NP predictions, and molecular docking validations. Ammijin, O-isopentenylhalfordinol, clionasterol, and fenretinide demonstrated notable binding affinity toward key AD-associated targets, show stronger affinity internal standards used in the study (donepezil and rivastigmine). Protein-protein interaction (PPI) analysis, Gene Ontology (GO), and KEGG pathway enrichment analysis showed that these compounds may influence critical pathological pathways involved in AD progression. The findings provide insight into the multi-targeted potential of AM bioactives against AD. Our results not only provided experimental justification for the ethnomedicinal use of AM as a neuroprotectant but also revealed key bioactives and targeted pathways that could be exploited for developing new plant-based therapeutic approaches for AD management. Further in-vitro and in-vivo investigations are necessary to validate these results and explore their practical applications.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00559-x.},
}

@article {pmid41613635,
year = {2026},
author = {Roy, G and Lingaraj, P and Periyasamy, TS and Kasivishwanathan, A and Sekar, N and Lakshmanan, H},
title = {Structure-based molecular docking and molecular dynamics simulation of phytoconstituents from Senecio species as potential acetylcholinesterase inhibitors targeting Alzheimer's disease.},
journal = {In silico pharmacology},
volume = {14},
number = {1},
pages = {46},
pmid = {41613635},
issn = {2193-9616},
abstract = {UNLABELLED: Alzheimer's disease (AD) is a neurodegenerative condition most often occurring in aged individuals and displaying symptoms of memory impairment, cognitive decline, and behavioral disturbances. With a significant reduction in acetylcholine levels, the disruption of the cholinergic system is an essential part of AD pathogenesis. By increasing the availability of acetylcholine and thus enhancing cholinergic transmission, acetylcholinesterase inhibitors (AChEIs) like galantamine, donepezil, and rivastigmine are employed to alleviate symptoms. In this study, the prospect of phytoconstituents of Senecio species collected from various literature (GC-MS and LC-MS data) as inhibitors of acetylcholinesterase (AchE) is investigated. A total of 250 compounds were screened for ADMET using SwissADME database. Out of these 42 were eligible for the docking study. The docking results revealed that 2 compounds (Piperitol [4EY7-PIP]) and (4R)-4-hydroxy-4,5,5-trimethyl-3-[(E)-3-oxobut-1-enyl]cyclohex-2-en-1-one [xxx]) showed stronger binding to the AchE receptor than the standard drug, donepezil. Further, the compounds were subjected to Molecular dynamics simulations for 100ns. The results revealed that these molecules significantly stabilized proteins in different parameters, such as RMSD, RMSF, Rg, SASA, and MM-PBSA. The inspection of solvent interaction, structural compactness, and molecular flexibility underlined the desirable interaction and dynamic stability of 4EY7-PIP. Steered Molecular Dynamics (SMD) uses externally applied forces to probe molecular interactions, conformational changes, and energy landscapes beyond the reach of conventional MD. Based on these findings, Senecio species most prominent phytoconstituent can be employed as a therapeutic agent against Alzheimer's disease, but more experimental studies are required to establish its value and therapeutic benefits.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00556-0.},
}

@article {pmid41613276,
year = {2026},
author = {Zeldich, D and Cheng, CH and Guan, Y and Narain, S and Koo, BB},
title = {Apolipoprotein E4 and its later-life health effects on the multiple sclerosis population.},
journal = {Multiple sclerosis journal - experimental, translational and clinical},
volume = {12},
number = {1},
pages = {20552173251387833},
pmid = {41613276},
issn = {2055-2173},
abstract = {BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic resonance imaging (MRI) metrics.

RESULTS: MS-E4 patients exhibited worse outcomes, including thinner RNFL, higher blood glial fibrillary acidic protein (GFAP) and neurofilament light chain levels, slower cognitive reaction times, and more white matter hyperintensities. GFAP had significant interactions between MS and APOE4 status, correlating with neurodegenerative markers.

DISCUSSION: APOE4 exacerbates neurodegeneration and neuroinflammation in MS, evident in retinal OCT, cognitive testing, and MRI findings. Similar effects were observed in healthy APOE4 carriers. These results highlight the utility of multi-domain biomarkers for MS diagnosis and long-term management, emphasizing less invasive tools for monitoring disease progression.},
}

@article {pmid41613271,
year = {2025},
author = {Amawi, RM and Ashmawy, NS},
title = {GC-MS-based metabolic profiling of essential oils from Citrus paradisi, Lawsonia inermis, and Ruta graveolens and assessment of their acetylcholinesterase inhibitory potential.},
journal = {Frontiers in chemistry},
volume = {13},
number = {},
pages = {1761973},
pmid = {41613271},
issn = {2296-2646},
abstract = {INTRODUCTION: Plant-derived essential oils (EOs) are rich sources of bioactive compounds, some of which exhibit acetylcholinesterase (AChE) inhibitory activity and may offer therapeutic potential for the management of Alzheimer's disease (AD). This study aimed to evaluate the chemical composition and AChE inhibitory potential of essential oils extracted from Citrus paradisi (grapefruit), Lawsonia inermis (henna), and Ruta graveolens (sadab).

METHODS: Essential oils were obtained by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC-MS) to identify their chemical constituents. AChE inhibitory activity was determined using Ellman's colorimetric assay, and IC50 values were calculated to assess inhibitory potency.

RESULTS: A total of 63 metabolites were identified across the three essential oils, accounting for approximately 90% of their total composition. Grapefruit EO was predominantly composed of limonene (89.94%), henna EO was rich in phytol (41.42%) and limonene (23.02%), while sadab EO was characterized by 1-hexadecanol acetate (26.39%) and phytol (20.54%). Grapefruit EO exhibited the strongest AChE inhibitory activity (IC50 = 12.62 ± 0.48 μg/mL), followed by henna EO (IC50 = 43.90 ± 0.97 μg/mL), whereas sadab EO showed negligible inhibition.

DISCUSSION: The notable AChE inhibitory activity observed in grapefruit and henna essential oils is likely attributable to their high terpenoid content. These findings suggest that selected plant-derived essential oils may represent promising natural candidates for the prevention or management of neurodegenerative disorders such as Alzheimer's disease.},
}

@article {pmid41613186,
year = {2025},
author = {An, W and Jin, Z and Li, Y},
title = {Dual role of exosomes in neurodegenerative diseases: a molecular bridge between neuroinflammation and transmission of pathological proteins.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1708655},
pmid = {41613186},
issn = {1664-2295},
abstract = {Neurodegenerative diseases (NDDs) are complex disorders characterized by the progressive loss of neuronal function. Their pathological mechanisms involve multiple levels, including neuroinflammation, abnormal protein aggregation, and disrupted cell signaling. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis (MS), and prion diseases not only severely impact patients' quality of life but also pose significant challenges for medical research due to their complex pathogenesis and the lack of effective treatments. In recent years, extracellular vesicles (EVs), particularly exosomes, have garnered increasing attention for their critical role in cell-to-cell communication. Exosomes are membrane-enclosed nanovesicles approximately 30-150 nm in diameter that can carry proteins, lipids, nucleic acids, and other bioactive molecules, influencing recipient cells through paracrine or distant signaling. This review aims to summarize the roles of exosomes as mediators of neuroinflammation and as vehicles for intercellular transmission of pathogenic proteins in neurodegenerative diseases.},
}

@article {pmid41613025,
year = {2026},
author = {Akcin, R and Tutuncu, M and Sakallı, NK and Apaydın, H and Bozluolçay, M and Can, G and Soysal, A and Sirekbasan, S and Dinc, HO and Saribas, S and Kocazeybek, B},
title = {Evaluation of Seropositivity Developed Against Specific Antigens of Helicobacter pylori in Neurodegenerative Diseases.},
journal = {Noro psikiyatri arsivi},
volume = {63},
number = {},
pages = {65-72},
pmid = {41613025},
issn = {1300-0667},
abstract = {INTRODUCTION: It is suggested that Helicobacter pylori (Hp) can reach the brain via the oral-nasal-olfactory route, through Hp-infected monocytes in the disrupted blood-brain barrier (BBB), or through a rapid retrograde neural network leading to neurodegeneration from the gastrointestinal tract (GIS) and may lead to neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD) and Multiple sclerosis (MS). In this study, we aimed to evaluate the possible immunopathogenesis relationship between Hp-specific antigens and neurodegenerative diseases by determining the frequency of seropositivity against different specific antigens of Hp in diseases such as AD, PD and MS.

METHODS: In our cross-sectional, retrospective case-control study, the immunoreactivity frequencies of Hp-specific and non-specific CagA (p120), VacA (p95), p75, FSH (p67), UreB (p66), HSP homolog (p57), flagellin (p54), p50, p41, p33, OMP (p30), UreA (p29), p26, OMP (p19), p17 antigens were determined by Western Blot method in 36 AD, 35 PD, 91 MS cases with Hp-IgG reactivity, and 55 controls without a neurodegenerative/demyelinating by ELISA method.

RESULTS: No significant difference was found between the immunoreactivity frequencies of Hp antigens between AD and control groups (p>0.05). In the multivariate logistic analysis performed for PD cases, age ≥ 50 and immunoreactivity frequency of p19 were found to be independent risk factors (OR: 36.752, p<0.05) (OR: 5.570, p<0.05). In MS cases, immunoreactivity frequency of p17 antigen was found to be a risk factor (OR: 2.646, p<0.05). In addition, the mean level of Hp-IgG reactivity was found to be negatively associated with MS development (indicating an inverse correlation) in the control group compared to the MS group (OR: 0.585, p < 0.05). Furthermore, logistic regression analysis in the total study group revealed that the immunoreactivity frequency of the p17 antigen was identified as a risk factor for MS (OR: 2.438, p<0.05).

CONCLUSION: Our data on AD cases are insufficient. In PD cases, the significantly higher frequency of immunoreactivity to the Hp-p19 antigen in individuals aged ≥50 years (OR=5.570) is noteworthy. In the MS group, the significantly high detection of Hp p17 antigen and its presence as a risk factor (OR=2.646), and the significantly high detection of p26 antigen suggest the relationship between these antigens and the MS development process. However, it is a fact that new and many prospective cohort-based case-control studies are needed to reveal this more clearly.},
}

@article {pmid41613013,
year = {2026},
author = {Aravena, JM and Saguez, R and Sandoval, MH and Herrera, C and Albala, C and Fuentes, P},
title = {Willing, but unequally: Indigenous identity influences participation in Alzheimer's disease biomarker research in Chile.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70261},
pmid = {41613013},
issn = {2352-8729},
abstract = {INTRODUCTION: This study aimed to compare the willingness to use Alzheimer's disease (AD) predictive-diagnostic procedures between Mapuche (Indigenous) and non-Indigenous older adults in Chile.

METHODS: We conducted a cross-sectional study including Mapuche (n = 167) and non-Indigenous (n = 248) older adults. Willingness to undergo five predictive-diagnostic procedures (AD risk test, neuropsychological assessment, blood test, brain imaging, and cerebrospinal fluid analysis) was evaluated. Logistic regression models were used to identify factors associated with willingness.

RESULTS: Overall willingness was high, except for cerebrospinal fluid testing (39.1%). In fully adjusted models, Mapuche participants were significantly less willing to undergo neuropsychological assessment (77.8% vs. 92.3%), blood testing (68.3% vs. 89.9%), and brain imaging (73.1% vs. 84.3%). Key determinants of willingness varied by ethnic group and included age, sex, AD-related worry, social determinants, and number of dementia risk factors.

DISCUSSION: Despite high overall willingness, ethnic identity and psychosocial factors significantly influenced receptiveness to AD predictive-diagnostic procedures.

HIGHLIGHTS: Indigenous populations in high-income countries face a higher risk of dementia, making Alzheimer's disease (AD) biomarker and diagnostic research a critical priority in these groups.Despite this, Indigenous and Latin American populations remain among the most underrepresented in dementia research.In a sample of Indigenous (Mapuche) and non-Indigenous older adults in Chile, most participants reported willingness to use AD biomarkers and diagnostic procedures.In fully adjusted models, Mapuche individuals were significantly less willing to undergo neuropsychological testing, blood tests, and brain imaging for AD risk prediction.Willingness to use AD biomarkers varied by ethnic identity and was influenced by age, social determinants, and attitudes toward AD.},
}

@article {pmid41612939,
year = {2026},
author = {Pang, H and Frontera, J and Jiang, L and Li, C and Boutajangout, A and Sun, Z and Debure, L and Ghuman, M and Vedvyas, A and Masurkar, AV and Wisniewski, T and Ge, Y},
title = {Choroid plexus alterations in long COVID and their associations with Alzheimer's disease risks.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71020},
doi = {10.1002/alz.71020},
pmid = {41612939},
issn = {1552-5279},
support = {R01AG077422//The National Institutes of Health/National Institute on Aging/ ; U24 NS135568/NS/NINDS NIH HHS/United States ; P30AG066512//The National Institutes of Health/National Institute on Aging/ ; R01AG077422/GF/NIH HHS/United States ; U24 NS135568/GF/NIH HHS/United States ; P30AG066512/GF/NIH HHS/United States ; },
mesh = {Humans ; *Choroid Plexus/diagnostic imaging/pathology ; *Alzheimer Disease/diagnostic imaging ; Female ; Male ; Aged ; *COVID-19/complications/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Cerebrovascular Circulation/physiology ; tau Proteins/blood ; Biomarkers/blood ; Middle Aged ; Aged, 80 and over ; Cognitive Dysfunction ; },
abstract = {INTRODUCTION: Choroid plexus (ChP) enlargement is a neuroimaging biomarker of neuroinflammation and neurodegeneration. However, evidence of ChP structural and perfusion alterations in long coronavirus disease (COVID) and their clinical relevance remains limited.

METHODS: This study included 86 long COVID, 67 recovered COVID, and 26 COVID-negative healthy controls (HCs). ChP volume and cerebral blood flow (CBF) were quantified, and their associations with Alzheimer's disease (AD) symptoms and plasma biomarkers were examined.

RESULTS: Both patient groups showed higher ChP volume and lower CBF than HC. Relative to recovered COVID, long COVID patients had a larger ChP volume, but no significant difference in CBF. ChP volume correlated positively with glial fibrillary acidic protein (r = 0.35) and phosphorylated tau217 (p-tau217; r = 0.54), while CBF correlated negatively with p-tau217 (r = -0.56). Both ChP volume and CBF were associated with cognitive decline measured with Mini-Mental State Examination and Clinical Dementia Rating.

DISCUSSION: These findings suggest that ChP differences in long COVID are associated with AD-related cognitive decline and increased plasma biomarkers.

HIGHLIGHTS: Long coronavirus disease (COVID) patients show choroid plexus (ChP) enlargement and reduced cerebral blood flow. ChP alterations are associated with Alzheimer's disease (AD)-related symptoms and plasma biomarker changes. ChP alterations on magnetic resonance imaging may serve as imaging markers for tracking neurological symptoms and AD-related pathology in post-COVID patients.},
}

Humans
*Choroid Plexus/diagnostic imaging/pathology
*Alzheimer Disease/diagnostic imaging
Female
Male
Aged
*COVID-19/complications/diagnostic imaging/pathology
Magnetic Resonance Imaging
Cerebrovascular Circulation/physiology
tau Proteins/blood
Biomarkers/blood
Middle Aged
Aged, 80 and over
Cognitive Dysfunction

@article {pmid41612924,
year = {2026},
author = {Cha, WJ and Chumin, EJ and Yi, D and Byun, MS and Jung, JH and Ahn, H and Jung, G and Kim, YK and Lee, YS and Kang, KM and Sohn, CH and Risacher, SL and Sporns, O and Nho, K and Saykin, AJ and Lee, DY and , },
title = {Amyloid-related default mode network hyperconnectivity and longitudinal decline in network distinctiveness in preclinical Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71025},
doi = {10.1002/alz.71025},
pmid = {41612924},
issn = {1552-5279},
support = {//New Faculty Startup Fund from Seoul National University/ ; RS-2022-00165636//National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT/ ; 2014M3C7A1046042//National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT/ ; HI18C0630//Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare/ ; HI19C0149//Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare/ ; RS-2023-KH136195//Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT/ ; U01AG072177//National Institutes of Health (USA)/ ; P30AG072976//National Institutes of Health (USA)/ ; R01AG075959//National Institutes of Health (USA)/ ; R01AG082348//National Institutes of Health (USA)/ ; R01AG081951//National Institutes of Health (USA)/ ; R01AG057739//National Institutes of Health (USA)/ ; R01AG070883//National Institutes of Health (USA)/ ; U01AG024904//National Institutes of Health (USA)/ ; R01LM013463//National Institutes of Health (USA)/ ; T32AG071444//National Institutes of Health (USA)/ ; U24AG074855//National Institutes of Health (USA)/ ; U01AG068057//National Institutes of Health (USA)/ ; U01AG24904//National Institutes of Health (USA)/ ; U19AG074879//National Institutes of Health (USA)/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/physiopathology/metabolism ; Male ; Female ; Magnetic Resonance Imaging ; Aged ; *Default Mode Network/diagnostic imaging/physiopathology/metabolism ; *Cognitive Dysfunction/diagnostic imaging/physiopathology ; *Amyloid beta-Peptides/metabolism ; Longitudinal Studies ; Cross-Sectional Studies ; *Brain/diagnostic imaging/physiopathology ; *Nerve Net/diagnostic imaging/physiopathology ; },
abstract = {INTRODUCTION: We investigated stage-specific alterations in functional connectivity (FC) of the default mode network (DMN) across the Alzheimer's disease (AD) continuum and tested whether early amyloid beta (Aβ)-related changes in within-DMN FC (DMN-FCwithin) predicted longitudinal alterations in DMN between-network connectivity (DMN-FCbetween).

METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were analyzed from 396 older adults: Aβ-negative cognitively normal (CN-, n = 213), Aβ-positive CN (CN+, n = 37), Aβ-positive mild cognitive impairment (MCI+, n = 72), and Aβ-positive dementia (dementia+, n = 74). Cross-sectional analyses compared DMN-FC across groups and examined associations with continuous Aβ burden at baseline. Longitudinal analyses in 171 CN participants with 2-year follow-up (CN-, n = 147; CN+, n = 24) tested whether baseline DMN-FCwithin predicted changes in DMN-FCbetween.

RESULTS: CN+ individuals showed elevated DMN-FCwithin and reduced DMN-FCbetween relative to other groups. In CN, Aβ burden was associated with FC, and baseline DMN-FCwithin predicted longitudinal increases in DMN-FCbetween only in CN+.

DISCUSSION: Aβ-related hyperconnectivity characterizes preclinical AD and may drive progressive network-level vulnerability.

HIGHLIGHTS: Cognitively normal amyloid beta (Aβ)-positive (CN+) individuals showed stronger connectivity within the default mode network (DMN). CN+ individuals also showed weaker links between the DMN and other brain networks. Amyloid was not linked to connectivity changes in cognitively impaired adults. Higher DMN connectivity predicted broader network changes in CN+ individuals.},
}

Humans
*Alzheimer Disease/diagnostic imaging/physiopathology/metabolism
Male
Female
Magnetic Resonance Imaging
Aged
*Default Mode Network/diagnostic imaging/physiopathology/metabolism
*Cognitive Dysfunction/diagnostic imaging/physiopathology
*Amyloid beta-Peptides/metabolism
Longitudinal Studies
Cross-Sectional Studies
*Brain/diagnostic imaging/physiopathology
*Nerve Net/diagnostic imaging/physiopathology

@article {pmid41612921,
year = {2026},
author = {Daven, M and Bass, DM and Deaner, N and Sawyer, RJ and Evertson, L and Reuben, DB and , },
title = {A framework for implementing high-quality dementia care navigation: recommendations from the Alzheimer's Association Dementia Care Navigation Roundtable.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71102},
doi = {10.1002/alz.71102},
pmid = {41612921},
issn = {1552-5279},
support = {//Biogen/ ; //Cleveland Clinic/ ; //Elbi, John A. Hartford Association, Lilly/ ; //Novo Nordisk/ ; //Otsuka, Rippl, Synapticure/ ; },
mesh = {Humans ; *Dementia/therapy ; *Patient Navigation/standards ; United States ; *Alzheimer Disease/therapy ; *Quality of Health Care ; Patient-Centered Care ; },
abstract = {In 2023, the Alzheimer's Association launched the Dementia Care Navigation (DCN) Roundtable, a diverse group of dementia experts to provide strategic guidance to organizations implementing person- and family-centered DCN services. Three initial areas to enhance DCN and its implementation were identified: (1) improving the quality of DCN by further defining navigator duties, roles, and care pathways; (2) establishing standards for DCN training to ensure quality, consistency, and person- and family-centeredness; and (3) developing a sustainable business case to ensure its financial viability. The roundtable clarified navigator responsibilities, encouraged the use of community partners as DCN providers, and aligned DCN services with Medicare's Guiding and Improved Dementia Experience GUIDE model. The roundtable recommended that all team members undergo training to acquire the necessary knowledge to provide effective and compassionate care. Building a sustainable business case requires demonstrating both financial and non-financial value, engaging payers, and aligning DCN with healthcare performance metrics. HIGHLIGHTS: Recommendations were based on the GUIDE model and 7 Essential Principles of DCN. Dementia care team members should have defined roles across care delivery domains. Dementia care navigators should be trained in person- and family-centered care. A sustainable business case should demonstrate financial and non-financial value.},
}

Humans
*Dementia/therapy
*Patient Navigation/standards
United States
*Alzheimer Disease/therapy
*Quality of Health Care
Patient-Centered Care

@article {pmid41612914,
year = {2026},
author = {Zheng, W and Jiang, Y and Wong, HY and Wong, WW and Cheng, LKW and Cheng, EYL and Wong, BWY and Lo, RMN and Leung, SK and Ip, FC and Yuen, JKY and Shea, YF and Wong, WM and Shum, CK and Wai, HM and Mok, VCT and Kwok, TCY and Mok, KY and Heslegrave, A and Hardy, J and Zetterberg, H and Fu, AKY and Ip, NY},
title = {Targeted blood proteome profiling using NULISAseq identifies a high-performance biomarker panel for Aβ pathology quantification and staging.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71179},
doi = {10.1002/alz.71179},
pmid = {41612914},
issn = {1552-5279},
support = {C6027-19GF//Research Grants Council of Hong Kong (the Collaborative Research Fund)/ ; T13-605/18W//Research Grants Council of Hong Kong (Theme-Based Research Scheme)/ ; HKUST16103122//Research Grants Council of Hong Kong (General Research Fund)/ ; HKUST16104624//Research Grants Council of Hong Kong (General Research Fund)/ ; HKUST16102824//Research Grants Council of Hong Kong (General Research Fund)/ ; AoE/M-604/16//Areas of Excellence Scheme of the University Grants Committee/ ; ITCPD/17-9//InnoHK Innovation and Technology Commission of the Hong Kong Special Administrative Region Government/ ; JLFS/M-604/24//SIAT-HKUST Joint Laboratory for Brain Science/ ; 2023B1212120004//Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders/ ; },
mesh = {Humans ; *Alzheimer Disease/blood/pathology/diagnosis ; *Biomarkers/blood ; *Amyloid beta-Peptides/blood/metabolism ; Male ; Female ; Aged ; *Proteome/metabolism ; Positron-Emission Tomography ; *Plaque, Amyloid/pathology/blood ; Disease Progression ; Hong Kong ; Cohort Studies ; *Blood Proteins/metabolism ; Middle Aged ; Proteomics/methods ; },
abstract = {INTRODUCTION: While current blood-based biomarkers for Alzheimer's disease (AD) are effective for determining amyloid beta (Aβ) pathology positivity/negativity, they are insufficient for quantifying Aβ plaque deposition.

METHODS: We profiled 325 plasma proteins in a Hong Kong Chinese cohort using the Nucleic Acid Linked Immuno‑Sandwich Assay (NULISAseq) platform. We analyzed the dysregulation trajectories of the blood proteome along Aβ pathology progression and used machine learning to develop a biomarker panel to quantify Aβ pathology.

RESULTS: We identified 43 blood proteins correlated with Aβ plaque accumulation and selected 8 proteins to construct a model. This model was strongly correlated with amyloid positron emission tomography Centiloid values (r = 0.89), enabling quantification of Aβ deposition and classification of early-stage pathology (area under the curve = 0.93).

DISCUSSION: This study provides a systematic profile of dynamic protein alterations during Aβ pathology progression. Moreover, we developed a biomarker assay that accurately quantifies Aβ pathology, offering a potential tool to facilitate early screening and monitoring of amyloid pathology.},
}

Humans
*Alzheimer Disease/blood/pathology/diagnosis
*Biomarkers/blood
*Amyloid beta-Peptides/blood/metabolism
Male
Female
Aged
*Proteome/metabolism
Positron-Emission Tomography
*Plaque, Amyloid/pathology/blood
Disease Progression
Hong Kong
Cohort Studies
*Blood Proteins/metabolism
Middle Aged
Proteomics/methods

@article {pmid41612908,
year = {2026},
author = {Hickman, SE and Miech, EJ and Stump, TE and Tu, W and Unroe, KT},
title = {Difference-Makers for Robust Implementation of a Nursing Home Advance Care Planning Embedded Pragmatic Clinical Trial.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.70289},
pmid = {41612908},
issn = {1532-5415},
support = {R33AG057463/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: Embedded pragmatic clinical trials are an ideal way to develop and evaluate evidence-based interventions in the nursing home (NH) environment to facilitate streamlining implementation after study completion. However, there is minimal information available about the necessary and sufficient conditions of "difference makers" for robust implementation of pragmatic interventions in the NH setting.

METHODS: The "Aligning Patient Preferences-a Role Offering Alzheimer's patients, Caregivers, and Healthcare Providers Education and Support" (APPROACHES) embedded pragmatic trial is designed to test and evaluate a staff-led advance care planning (ACP) intervention for residents with dementia in 128 NHs (64 intervention, 64 control). Coincidence Analysis, a case-based approach to data analysis that draws upon Boolean algebra and set theory, was applied to identify key difference-makers for robust implementation. This analysis focused on the 44 intervention NHs that implemented at least one of two implementation processes: site visits and/or monthly calls.

RESULTS: Eighteen of 44 (41%) sites in the analysis robustly implemented the APPROACHES intervention as reflected by > 75% of residents having a documented ACP conversation. The Coincidence Analysis revealed two pathways directly linked with robust pragmatic implementation: (1) no executive director turnover during the observation period combined with site participation in monthly calls with peers; and (2) higher rates of baseline hospitalization (3.96-7.0 per 1000 resident-days alive) combined with a low number of certified beds. In contrast, leadership instability as reflected by administrator turnover, high number of certified beds, and a lack of participation in monthly calls with peers was associated with poorer performance.

DISCUSSION: Findings from this study suggest that leadership stability and engagement with peers were essential drivers of robust implementation of the APPROACHES ACP Specialist intervention. Coincidence Analysis is a useful tool for understanding how implementation conditions are associated with robust implementation in embedded pragmatic clinical trials.},
}

@article {pmid41612899,
year = {2026},
author = {Warren, SL and Moustafa, AA},
title = {Functional and Clinical: An Explainable Deep Learning Model for Multimodal Alzheimer's Disease Classification.},
journal = {Brain and behavior},
volume = {16},
number = {2},
pages = {e71240},
doi = {10.1002/brb3.71240},
pmid = {41612899},
issn = {2162-3279},
support = {//Australian Government Research Training Program/ ; },
mesh = {Humans ; *Alzheimer Disease/classification/diagnostic imaging/physiopathology/diagnosis ; *Deep Learning ; Magnetic Resonance Imaging/methods ; Aged ; Female ; Male ; Neural Networks, Computer ; Reproducibility of Results ; Brain/diagnostic imaging/physiopathology ; Aged, 80 and over ; },
abstract = {PURPOSE: Functional magnetic resonance imaging (fMRI) and deep learning models can classify Alzheimer's disease (AD) with high accuracy. These models are highly adaptable and work with a plethora of architectures, data types, and AD stages. However, fMRI deep learning models lack clinical application due to issues with small datasets, explainability, and reliability (e.g., data leakage).

METHODS: In this study, we address these issues using multimodal and explainable artificial intelligence (XAI) methods. Specifically, we overcome data size limitations by supplementing fMRI data with clinical tests, use a strict leave-one-out cross-validation regime to control for data leakage, and apply perturbation ranking to explain the importance of features in our model. Our 3D convolutional neural network model was trained and validated on 52 participants from ADNI using five clinical tests and fMRI of the default mode network.

FINDINGS: The resulting multimodal model classified AD from controls with an accuracy of 90% and outperformed the same architecture without clinical data (58% accuracy). Our feature rankings showed that clinical tests changed in importance within our model depending on the diagnostic group. For example, our model found the MoCA to be highly important for classifying controls but not for AD. This trend of feature importance was seen across almost all fMRI and clinical features.

CONCLUSION: Our model was highly accurate and highlighted the importance of combining fMRI and clinical data for AD classification. These findings have implications for the refinement of multimodal deep learning models; however, our small sample and need for external validation are also noted.},
}

Humans
*Alzheimer Disease/classification/diagnostic imaging/physiopathology/diagnosis
*Deep Learning
Magnetic Resonance Imaging/methods
Aged
Female
Male
Neural Networks, Computer
Reproducibility of Results
Brain/diagnostic imaging/physiopathology
Aged, 80 and over

@article {pmid41612858,
year = {2026},
author = {Garry, J and Tomlinson, M and Lohan, M},
title = {Exploring variation in research priorities generated by AI tools.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04037},
doi = {10.7189/jogh.16.04037},
pmid = {41612858},
issn = {2047-2986},
mesh = {Humans ; *Artificial Intelligence ; COVID-19/therapy ; HIV Infections/therapy ; Alzheimer Disease/therapy ; *Biomedical Research ; Neoplasms/therapy ; *Research ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Artificial intelligence (AI) tools based on large language models (LLMs) are being increasingly used by researchers and may play a role in health-related research priority-setting exercises (RPSEs). However, little is known about how these tools may differ in the types of research priorities they generate.

METHODS: We examined research priorities aimed at improving treatments for four diseases: cancer, COVID-19, HIV, and Alzheimer. We compared the outputs from five AI tools (DeepSeek, ChatGPT, Claude, Perplexity, and Gemini) using SBERT-BioBERT embeddings and cosine similarity scores, and assessed the stability of differences between them by re-running identical prompts and slightly modified versions.

RESULTS: We found that the outputs produced by Gemini were highly similar to those produced by the other tools. The two most different outputs were those produced by DeepSeek and Perplexity, whereby the former tended to emphasise technical medical issues, while the latter emphasised public health concerns. This substantive distinction between DeepSeek and Perplexity remained stable across repeated and tweaked prompts.

CONCLUSIONS: Our exploratory analysis suggests that Gemini performs well for researchers who prefer to generate health-related research priorities using a single AI model. For those planning to draw on multiple models, Perplexity and DeepSeek offer complementary perspectives.},
}

Humans
*Artificial Intelligence
COVID-19/therapy
HIV Infections/therapy
Alzheimer Disease/therapy
*Biomedical Research
Neoplasms/therapy
*Research
SARS-CoV-2

@article {pmid41612799,
year = {2026},
author = {Al-Twaijry, N and Almajhad, DA and Al-Bagmi, MS and Alafaleq, N and Alshehri, E and Alzharani, AA and Alokail, MS and Aldobiyan, I and Albahili, RA and Khan, MS and Jali, BR},
title = {Exploring insulin aggregation at neutral pH and its inhibition via caffeic acid: a biophysical and bioinformatics analysis.},
journal = {Journal of biomolecular structure & dynamics},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/07391102.2026.2619872},
pmid = {41612799},
issn = {1538-0254},
abstract = {This study aimed to induce fibril formation in human insulin under physiological conditions and to investigate the inhibitory potential of caffeic acid (CA) on these fibrils in-vitro. Various techniques including circular dichroism (CD) spectroscopy, Thioflavin T, ANS fluorescence, Rayleigh light scattering (RLS), and turbidity analysis were conducted to elucidate fibril formation and CA inhibition potential. Fibril formation in insulin was induced by heating (37 °C) and agitation (600 rpm) significantly increased (27.01-fold) the ThT binding after 120 h of incubation. Aggregation also increased turbidity and enhanced RLS fluorescence at 350 nm. Secondary structure analysis revealed at loss of α-helical content and a concomitant increase in β-sheet content in human insulin following aggregation. The presence of varying concentrations of CA resulted in fewer perturbations in the secondary structure of insulin compared with the aggregated insulin sample. Fibril formation was also reduced (80%) in the presence of CA (500 µM). To gain insight, the biophysical interactions between CA and insulin were studied. CA showed moderate affinity (5.54 × 10[3] M[-1]) towards insulin in static quenching mode. The positive ΔH and ΔS values obtained indicate that the reaction was driven by hydrophobic interactions and the negative value of ΔG indicates a spontaneous reaction between the complexes. Docking analysis showed the interaction of CA with various amino acids of insulin via H-bonds, van der Waals forces, and hydrophobic interactions. Molecular simulations of RMSD, RMSF, and Rg showed that CA formed a stable complex with insulin.},
}

@article {pmid41612616,
year = {2026},
author = {Abu-Amara, H and Zhao, W and Li, Z and Leung, YY and Schellenberg, GD and Wang, LS and Dey, AB and Dey, S and Zhou, X and Gross, AL and Lee, J and Kardia, SLR and Smith, JA},
title = {Indian-enriched genetic variants are associated with cognitive function.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71115},
doi = {10.1002/alz.71115},
pmid = {41612616},
issn = {1552-5279},
support = {R01 AG051125/AG/NIA NIH HHS/United States ; U01 AG064948/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Cognition/physiology ; *Dementia/genetics ; *Genetic Predisposition to Disease/genetics ; *Genetic Variation/genetics ; Genome-Wide Association Study ; India ; Longitudinal Studies ; Risk Factors ; White People/genetics ; *South Asian People/genetics ; },
abstract = {INTRODUCTION: Little is known about genetic risk factors for dementia in South Asians. Examining genetic variants that occur at higher frequency in India compared to other ancestries (i.e., Indian enriched variants) may identify genetic associations with cognitive function that are potentially unique to the Indian population.

METHODS: We examined whether 3.43 million variants enriched in India compared to European (EA), East Asian (EAS), and African (AFR) ancestries were associated with seven measures of cognitive function in 2680 older adults from the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD).

RESULTS: Identified Indian-enriched variants were largely near loci previously associated with neuropsychiatric traits, N-acetyltaurine levels, educational attainment, and cardiovascular risk factors for dementia. Several variants near genes previously associated with intellectual disabilities and synaptic function exhibited sex-specific effects.

DISCUSSION: Indian-enriched variants may play a significant role in cognitive function in South Asians living in India.

HIGHLIGHTS: Some cognitive function-associated variants are unique to, or more common in, India. Implicated genes were in cardiovascular, neurocognitive, and inflammatory pathways. Some Indian-enriched genetic variants demonstrate sex-specific effects.},
}

Aged
Aged, 80 and over
Female
Humans
Male
*Cognition/physiology
*Dementia/genetics
*Genetic Predisposition to Disease/genetics
*Genetic Variation/genetics
Genome-Wide Association Study
India
Longitudinal Studies
Risk Factors
White People/genetics
*South Asian People/genetics

@article {pmid41612558,
year = {2026},
author = {Jansson, D and Shofer, J and Colasurdo, E and Schindler, A and Li, G and Adler, CH and Balcer, L and Bernick, C and Daneshvar, D and Katz, D and McClean, M and Mez, J and Palmisano, J and Ashton, N and Blennow, K and Zetterberg, H and Tripodis, Y and Alosco, ML and Cummings, JL and Reiman, EM and Shenton, M and Stern, RA and Iliff, J and Peskind, ER and , },
title = {Alterations in CSF Amyloid-β and Tau Biomarkers in Former College and Professional American Football Players: Findings from the DIAGNOSE CTE Research Project.},
journal = {Journal of neurotrauma},
volume = {},
number = {},
pages = {8977151251390520},
doi = {10.1177/08977151251390520},
pmid = {41612558},
issn = {1557-9042},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem, but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer's disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). CSF was collected under controlled conditions using collection, processing, and cryostorage kits provided by the DIAGNOSE CTE Research Project Biomarker Core, and concentrations of Aβ40, Aβ42, tTau, and pTau (pTau181, pTau217, pTau231) were measured at the University of Gothenburg, Sweden, using immunoassays. Associations between CSF biomarker levels with football history, and diagnosis of traumatic encephalopathy syndrome (TES) were examined using linear regression, and corrected for age, education, APOE-ε4 allele status, race, and body mass index. Our analysis revealed that football exposure affected both CSF Aβ40 (p = 0.039) and Aβ42 (p = 0.038), particularly among those under 60 years of age in the PRO compared to the UE exposure group. Among former football players, estimates of RHI exposure were not generally associated with CSF Aβ, tTau, and pTau biomarker levels. CSF Aβ40 (p = 0.0041) and Aβ42 (p = 0.011) were lower in former football players with TES diagnosis compared to unexposed participants, although CSF Aβ, tTau, and pTau biomarker levels did not differ between former players with and without a TES diagnosis. Among former football players, reduced CSF Aβ40 (p = 0.011) and Aβ42 (p = 6e-04) were observed in those with cognitive impairment compared to those with neurobehavioral dysregulation. The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.},
}

@article {pmid41612483,
year = {2026},
author = {Kang, SH and Kim, S and Kim, YJ and Yoo, H and Lee, EH and Jang, H and Shin, D and Yun, J and Kim, JP and Kim, HJ and Na, DL and Zetterberg, H and Blennow, K and Gonzalez-Ortiz, F and Ashton, NJ and Day, TA and Duering, M and Koh, SB and Kim, SY and Kim, EY and Kim, ST and Sohn, B and Seo, SW},
title = {Glymphatic dysfunction links vascular pathology to Alzheimer's biomarkers and cognitive decline.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01964-2},
pmid = {41612483},
issn = {1758-9193},
abstract = {BACKGROUND: Vascular damage, including cerebral amyloid angiopathy (CAA) and non-amyloid cerebral small vessel disease (CSVD), has been linked to glymphatic dysfunction, which may contribute to Alzheimer's disease (AD) pathology and cognitive decline. We investigated the associations among vascular damage, glymphatic function measured by the DTI-ALPS (Diffusion Tensor Imaging-Analysis Along the Perivascular Space) index, AD plasma biomarkers, and cognitive decline.

METHODS: This study includes 1,249 participants recruited from Samsung Medical Center. We performed linear regression analysis to identify factors associated with the DTI-ALPS index. Further, linear regression analysis with vascular imaging markers, including CAA and CSVD summary scores, as predictors and DTI-ALPS index as an outcome was performed to investigate the effect of vascular pathology on glymphatic function. We conducted mediation analyses to investigate whether the DTI-ALPS index mediates the effect of vascular imaging markers on plasma biomarkers (phosphorylated tau 217 [p-tau 217], glial fibrillary acidic protein [GFAP], and neurofilament light chain [NFL]). Additionally, mediation analyses with the DTI-ALPS index as a predictor, each plasma biomarker as a mediator, and annual MMSE or CDR-SOB change as an outcome to investigate whether plasma biomarkers mediate the effect of the DTI-ALPS index on longitudinal cognitive decline.

RESULTS: First, the DTI-ALPS index was negatively associated with both CAA (β [95% CI] = -0.163 [-0.214, -0.112], p < 0.0001) and CSVD (β [95% CI] = -0.195 [-0.247, -0.143], p < 0.0001) summary scores after controlling for age, sex, BMI status, and APOE genotype. Second, the DTI-ALPS index fully mediated the relationship between these vascular markers and p-tau 217 (CSVD summary score, indirect effect β [95% CI] = 0.016 [0.010, 0.023], p < 0.001; CAA summary score, indirect effect β [95% CI] = 0.013 [0.008, 0.020], p < 0.001) and GFAP (CSVD summary score, indirect effect β [95% CI] = 0.015 [0.008, 0.022], p < 0.001; CAA summary score, indirect effect β [95% CI] = 0.012 [0.007, 0.019], p < 0.001), while partially mediating the relationship for NFL, regardless of Aβ uptake on PET. Finally, the DTI-ALPS index was significantly associated with cognitive decline and this association was partially mediated by plasma biomarkers.

CONCLUSIONS: These findings highlight glymphatic dysfunction as a key mechanism linking vascular pathology with tau, inflammation and neurodegeneration, independent of Aβ uptakes.},
}

@article {pmid41612473,
year = {2026},
author = {Zou, W and Yick, LW and Kwan, JS and Zhang, Z and Xue, H and Chan, KH},
title = {Adiponectin deficiency drives cerebrovascular dysfunction and synergizes with amyloid-β to exacerbate alzheimer's pathology.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01968-y},
pmid = {41612473},
issn = {1758-9193},
abstract = {Cerebrovascular dysfunction (CVD) is increasingly recognized as a contributor to Alzheimer's disease (AD) progression. Adiponectin (APN), an adipocyte-derived hormone with vasoprotective properties in the periphery, has an unclear impact on AD-related cerebrovascular integrity. We showed that APN-deficient mice exhibited reduced resting cerebral blood flow (CBF), impaired neurovascular coupling (NVC), disrupted blood-brain barrier (BBB), and enhanced cerebral amyloid angiopathy (CAA), which are CVD characteristics that also observed in 5xFAD mice, a model of AD. Notably, APN-deficient 5xFAD mice displayed more severe CVD than 5xFAD mice alone. Transcriptomic analysis of brain endothelial cells (ECs) identified dysregulated biological processes and key signaling pathways underlying EC dysfunction. Importantly, the administration of APN restored CBF and NVC in 5xFAD mice, and prevented tight junction protein (TJP) loss and barrier breakdown in Aβ40-exposed primary ECs. These results highlight the potential of alleviating CVD through targeting ECs with APN as a promising therapeutic strategy to delay the onset and mitigate the progression of AD.},
}

@article {pmid41612321,
year = {2026},
author = {Pedersen, EK and Øksnebjerg, L and Waldemar, G and Janbek, J and Nielsen, A and Nielsen, TR},
title = {Validation of the Danish version of the Carer Experience Scale in family caregivers of people with dementia.},
journal = {Health and quality of life outcomes},
volume = {24},
number = {1},
pages = {14},
pmid = {41612321},
issn = {1477-7525},
mesh = {Humans ; *Caregivers/psychology ; *Dementia/nursing/therapy/psychology ; Denmark ; Female ; Male ; *Quality of Life/psychology ; Reproducibility of Results ; Surveys and Questionnaires/standards ; Aged ; Middle Aged ; Psychometrics ; Aged, 80 and over ; Adult ; },
abstract = {BACKGROUND: The Carer Experience Scale (CES) measures the caring experience, focusing on caregiver-related quality of life (QoL) rather than health-related QoL. We aimed to validate the Danish language version of CES in family caregivers of people with dementia in Denmark by assessing CES discriminative and convergent validity. Further, we aimed to establish the internal consistency and test-retest reliability of CES.

METHODS: A baseline questionnaire from the Danish DemTool intervention trial, including CES and five other measures of QoL and wellbeing was completed by 375 family caregivers of people with dementia. Discriminative validity was assessed by the ability of CES to discriminate between different caring contexts and levels of caregiver strain, as determined by Mann-Whitney U and Kruskal-Wallis H tests. Convergent validity was assessed by analyzing correlations using Spearman's rank correlation coefficients between the CES index and domain scores, and the 5-level EQ-5D version (EQ-5D-5L), European Quality of life visual analog scale (EQ VAS), Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D), World Health Organization Wellbeing Index (WHO-5), and the University of California, Los Angeles Three-Item Loneliness Scale (UCLA 3-item). Internal consistency was assessed using Cronbach's α and test-retest reliability was assessed using intraclass correlation coefficient (ICC) between two different time points.

RESULTS: The CES effectively distinguished between different levels of caregiver strain. Further, the CES was not affected by different caregiver and care recipient characteristics. Supporting convergent validity, the CES index was moderately correlated with NPI-D (ρ=-0.42), WHO-5 (ρ = 0.44), and UCLA 3-item (ρ=-0.40). The CES index was weakly correlated with EQ-5D-5L (ρ = 0.27), and EQ-VAS (ρ = 0.26). The CES showed low internal consistency (α = 0.53), but high test-retest reliability (ICC = 0.76).

CONCLUSION: The Danish version of CES demonstrated discriminative validity and acceptable psychometric properties, providing further evidence for its use in family caregivers of people with dementia.},
}

Humans
*Caregivers/psychology
*Dementia/nursing/therapy/psychology
Denmark
Female
Male
*Quality of Life/psychology
Reproducibility of Results
Surveys and Questionnaires/standards
Aged
Middle Aged
Psychometrics
Aged, 80 and over
Adult

@article {pmid41613446,
year = {2025},
author = {Sun, Y and Sun, J and Feng, Y and Zhang, Y and Li, J and Wang, F and Loznik, M and Tian, Y and Zhang, H and Herrmann, A and Liu, K and Zhang, C},
title = {Significant downregulation of Alzheimer's amyloid-β levels enabled by engineered DNA nanomaterials.},
journal = {Fundamental research},
volume = {5},
number = {5},
pages = {2241-2247},
pmid = {41613446},
issn = {2667-3258},
abstract = {Although there are no effective therapies to block or reverse Alzheimer's disease (AD) progression at present, a promising therapeutic strategy is to reduce levels of amyloid-β (Aβ) proteins, which drive the formation of amyloid plaque, a primary hallmark in AD brains. Herein, we report that amphiphilic lipid-DNA molecules (LD) were designed by incorporating a long alkyl chain into the nucleotide base. It significantly down-regulated Alzheimer's Aβ levels in vivo and in vitro. In contrast to small-molecule chemical drugs and antibody therapies, the assembled DNA nanoparticles allowed them to effectively cross the blood-brain barrier (BBB) and accumulate in the brain, increasing the therapeutic effects. Notably, lipid-DNA downregulated the levels of Aβ peptides significantly in vitro. AD mice model experiments demonstrated that the LD-treated groups exhibited a rapid cognition behavioral improvement, which was associated with brain engagement of LD and reduced Aβ levels. Thus, the molecularly engineered DNA nanomaterials effectively regulated Aβ peptides. This work might provide a promising DNA engineering strategy for AD treatment.},
}

@article {pmid41612173,
year = {2026},
author = {Yu, L and Zhao, M and Zhang, W and Lv, Z and Zhao, K and Li, H and Qi, Y and Peng, X and Zheng, Z and Zhang, W},
title = {Precise Aβ clearance and antioxidant therapy in Alzheimer's disease via photoacoustic imaging-guided palladium hydride nanosheet-mediated photothermal treatment.},
journal = {BMC neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12868-025-00994-0},
pmid = {41612173},
issn = {1471-2202},
}

@article {pmid41612095,
year = {2026},
author = {Chouhan, S and Ghai, D and Sandhu, R and Tripathi, SL},
title = {Smart assistive technologies for neurodisorders: A review on AI, IoT, and wearable systems for enhanced patient care.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {2},
pages = {211},
pmid = {41612095},
issn = {1590-3478},
abstract = {Neurological disorders of the brain and spinal cord affect millions of individuals worldwide and continue to rise in prevalence. Conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, spinal cord injury, and neurodevelopmental disorders disrupt cognitive, motor, and autonomic functions, severely impacting quality of life. This review provides an up-to-date and structured examination of neurological disorders and presents novel findings derived from a rigorous search strategy based on Boolean operators and PRISMA-aligned screening. A total of 154 peer-reviewed articles met the inclusion and exclusion criteria and were systematically analyzed. This paper also offers a comprehensive clinical categorization of neurological disorders and outlines their diagnostic and functional challenges. Then, it classifies the architecture of smart assistive technologies across four dimensions-neurological disorders, smart technologies, functional layers, and clinical outcomes-to establish a unified taxonomy for neuro-assistive research. Further, it presents three major smart assistive techniques used for neurological disorders: (i) AI-based techniques, including adaptive neuro-signal decoding algorithms and behavioural anomaly detection using hybrid deep learning; (ii) IoT-based techniques, consisting of context-aware multisensor fusion frameworks and edge-cloud collaborative health networks; and (iii) wearable system techniques that enable continuous, unobtrusive monitoring in real-world contexts. A detailed performance evaluation summarizes key metrics such as Detection Rate (DR%), Precision Rate (PR%), Recall Rate (RR%), and Processing Time (PT), highlighting how parameter variations influence practical deployment. Benchmark datasets are then encapsulated with descriptions of their features, sizes, and access links, enabling dataset-wise comparison and identification of suitable evaluation platforms for future research. This review also identifies current limitations and capabilities of existing smart assistive systems and synthesizes their implications for future directions. By highlighting gaps such as multimodal fusion challenges, data privacy constraints, and the need for adaptive models, this paper proposes a forward-looking framework to make neuro-assistive solutions more clinically accessible. Ultimately, this work advocates for connected, intelligent, and adaptive systems that advance diagnosis, monitoring, and rehabilitation for individuals with neurological disorders.},
}

@article {pmid41611873,
year = {2026},
author = {Chen, N and Ding, J and Xiang, M and Liu, Z and Cao, F},
title = {Frontier and hot topics in Magnetoencephalography(MEG) in neurological diseases.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {2},
pages = {210},
pmid = {41611873},
issn = {1590-3478},
support = {No.2021ZD0300503//Innovation Program for Quantum Science and Technology under Grant/ ; },
mesh = {*Magnetoencephalography/trends/methods ; Humans ; *Nervous System Diseases/physiopathology/diagnosis/diagnostic imaging ; Bibliometrics ; *Brain/physiopathology ; },
abstract = {Magnetoencephalography (MEG), a non-invasive neuroimaging technique with millisecond temporal resolution and millimeter spatial resolution, is an essential tool for investigating neurological disorders. This study conducted a systematic analysis of 4,040 relevant publications from the Web of Science database (2000-2024) using VOSviewer and CiteSpace to identify research hotspots and trends in MEG applications for neurological disorders over the past 24 years. The analysis revealed a steady annual increase in publications, and showed that the research evolved in three distinct phases: the early period (2000-2004) focused primarily on fundamental MEG principles, the intermediate period (2005-2015) shifted toward MEG signal analysis methods including network analysis, and the recent period (2016-2024) emphasized brain network functional connectivity analysis. Emerging research hotspots converged on the clinical application of analytical methods such as brain functional connectivity, encompassing areas such as the early diagnosis of Alzheimer's disease and preoperative evaluation for epilepsy. This study provided the first comprehensive bibliometric analysis of research hotspots and developmental trends in MEG applications for neurological disorders. These findings provided researchers with a clear understanding of the field's evolution and current landscape, thereby facilitating the rapid identification of promising research directions.},
}

*Magnetoencephalography/trends/methods
Humans
*Nervous System Diseases/physiopathology/diagnosis/diagnostic imaging
Bibliometrics
*Brain/physiopathology

@article {pmid41611738,
year = {2026},
author = {Carrasco-Gómez, M and García-Colomo, A and Cabrera-Álvarez, J and Bruña, R and Santos, A and Maestú, F},
title = {Dynamics of brain connectivity across the Alzheimer's disease spectrum through magnetoencephalography.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {3905},
pmid = {41611738},
issn = {2045-2322},
support = {FPU18/00517//Ministerio de Universidades, Spain/ ; PRE2019-087612//Ministerio de Universidades, Spain/ ; FPU2019-04251//Ministerio de Universidades, Spain/ ; SI2009-14415-C03-01//Ministerio de Economía y Competitividad, Spain/ ; B2017/BMD-3760//Comunidad de Madrid, Spain/ ; },
mesh = {Humans ; *Alzheimer Disease/physiopathology/diagnostic imaging ; *Magnetoencephalography/methods ; Male ; Female ; Aged ; *Cognitive Dysfunction/physiopathology ; *Brain/physiopathology/diagnostic imaging ; White Matter/physiopathology ; Middle Aged ; Gray Matter/physiopathology ; *Nerve Net/physiopathology ; Aged, 80 and over ; },
abstract = {Changes in static functional connectivity have been extensively linked to Alzheimer's Disease (AD), however, dynamic functional connectivity (dFC) across the AD continuum remains understudied. The current investigation leverages the high temporal resolution of MEG to dissect the dynamics of brain connectivity alterations across various stages of AD and their association with cognitive decline and structural brain changes. 321 participants were included, categorized into healthy control, subjective cognitive decline (SCD), and mild cognitive impairment (MCI) groups. Amplitude envelope correlation with leakage correction was calculated over MEG signals using a sliding window, and the correlation across epochs was studied to assess dFC. We explored dFC associations with cognitive scores, grey matter volume, and white matter fractal anisotropy. Whole-brain dFC declined along the AD continuum, especially in the alpha and beta bands, with pronounced reductions in the frontal and temporal lobes and default mode network regions. Moreover, these dFC changes correlated with cognitive decline and structural brain alterations. The present study underscores the relevance of dFC in capturing early temporal dynamic alterations, linking high-frequency activity in association cortices to white matter integrity and cognitive deterioration, thus highlighting the metric's potential as a sensitive marker of disease progression.},
}

Humans
*Alzheimer Disease/physiopathology/diagnostic imaging
*Magnetoencephalography/methods
Male
Female
Aged
*Cognitive Dysfunction/physiopathology
*Brain/physiopathology/diagnostic imaging
White Matter/physiopathology
Middle Aged
Gray Matter/physiopathology
*Nerve Net/physiopathology
Aged, 80 and over

@article {pmid41611638,
year = {2026},
author = {Tang, C and Yang, J and Lei, X and Zhang, M and Chen, Y and Peng, X and He, D},
title = {Association between brain volume and depression in Alzheimer's disease: Neuroimaging insights.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71120},
doi = {10.1002/alz.71120},
pmid = {41611638},
issn = {1552-5279},
support = {U24AG072122//National Institute on Aging and National Institutes of Health/ ; P30AG062429/AG/NIA NIH HHS/United States ; P30AG066468/AG/NIA NIH HHS/United States ; P30AG062421/AG/NIA NIH HHS/United States ; P30AG066509/AG/NIA NIH HHS/United States ; P30AG066514/AG/NIA NIH HHS/United States ; P30AG066530/AG/NIA NIH HHS/United States ; P30AG066507/AG/NIA NIH HHS/United States ; P30AG066444/AG/NIA NIH HHS/United States ; P30AG066518/AG/NIA NIH HHS/United States ; P30AG066512/AG/NIA NIH HHS/United States ; P30AG066462/AG/NIA NIH HHS/United States ; P30AG072979/AG/NIA NIH HHS/United States ; P30AG072972/AG/NIA NIH HHS/United States ; P30AG072976/AG/NIA NIH HHS/United States ; P30AG072975/AG/NIA NIH HHS/United States ; P30AG072978/AG/NIA NIH HHS/United States ; P30AG072977/AG/NIA NIH HHS/United States ; P30AG066519/AG/NIA NIH HHS/United States ; P30AG062677/AG/NIA NIH HHS/United States ; P30AG079280/AG/NIA NIH HHS/United States ; P30AG062422/AG/NIA NIH HHS/United States ; P30AG066511/AG/NIA NIH HHS/United States ; P30AG072946/AG/NIA NIH HHS/United States ; P30AG062715/AG/NIA NIH HHS/United States ; P30AG072973/AG/NIA NIH HHS/United States ; P30AG066506/AG/NIA NIH HHS/United States ; P30AG066508/AG/NIA NIH HHS/United States ; P30AG066515/AG/NIA NIH HHS/United States ; P30AG072947/AG/NIA NIH HHS/United States ; P30AG072931/AG/NIA NIH HHS/United States ; P30AG066546/AG/NIA NIH HHS/United States ; P20AG068024/AG/NIA NIH HHS/United States ; P20AG068053/AG/NIA NIH HHS/United States ; P20AG068077/AG/NIA NIH HHS/United States ; P20AG068082/AG/NIA NIH HHS/United States ; P30AG072958/AG/NIA NIH HHS/United States ; P30AG072959/AG/NIA NIH HHS/United States ; P30AG072980//Arizona Alzheimer's Center/ ; R01AG069453//Arizona Alzheimer's Center/ ; P30AG019610//Arizona Alzheimer's Center/ ; //and the State of Arizona which provided additional funding supporting our center/ ; P30AG013846//Boston University/ ; P30AG062428//Clevel and ADRC/ ; //Clevel and Clinic/ ; P20AG068053//Las Vegas/ ; P50AG008702//Columbia/ ; P30AG072958//Duke/UNCADRC/ ; P30AG066511//Emory University/ ; R01AG19771//Indiana University/ ; P30AG10133//Indiana University/ ; P30AG072976//Indiana University/ ; R01AG061788//Indiana University/ ; R01AG053993//Indiana University/ ; U01AG057195//Indiana University/ ; U19AG063911//Indiana University/ ; //and the Indiana University Department of Radiology and Imaging Sciences/ ; P30AG066507//Johns Hopkins/ ; P50AG016574//Mayo Clinic/ ; P30AG066514//Mount Sinai/ ; R01AG054110//Mount Sinai/ ; R01AG053509//Mount Sinai/ ; P30AG066512-01S2//New York University/ ; R01AG056031//New York University/ ; R01AG056531//New York University/ ; P30AG013854//North western University/ ; R01AG045571//North western University/ ; R56AG045571//North western University/ ; R01AG067781//North western University/ ; U19AG073153//North western University/ ; R01DC008552//North western University/ ; R01AG077444//North western University/ ; R01NS075075//North western University/ ; R01AG056258//North western University/ ; P30AG008017//Oregon Health and Science University/ ; R56AG074321//Oregon Health and Science University/ ; P30AG010161//Rush University/ ; P30AG066515//Stanford/ ; P50AG047366//Stanford/ ; P20//University of Alabama, Birmingham/ ; P30AG10129//University of California, Davis/ ; P30AG072972//University of California, Davis/ ; P50AG016573//University of California, Irvine/ ; P30AG062429//University of California, San Diego/ ; P30AG062422//University of California, San Francisco/ ; P30AG035982//University of Kansas/ ; P30AG028283-15S1//University of Kentucky/ ; P30AG053760//University of Michigan ADRC/ ; P30AG072931//University of Michigan ADRC/ ; 200775//Cure Alzheimer's Fund/ ; U19NS120384//Cure Alzheimer's Fund/ ; R01AG068338//Cure Alzheimer's Fund/ ; S10OD026738-01//Cure Alzheimer's Fund/ ; R01AG058724//Cure Alzheimer's Fund/ ; R35AG072262//Cure Alzheimer's Fund/ ; W81XWH2110743//Cure Alzheimer's Fund/ ; R01AG073235//Cure Alzheimer's Fund/ ; 1I01RX001534//Cure Alzheimer's Fund/ ; IRX001381//Cure Alzheimer's Fund/ ; P20AG068077//University of New Mexico/ ; 2019NF4100087335//University of Pennsylvania-State of PA project/ ; R01AG055005//Rooney Family Research Fund/ ; P50AG005133//University of Pittsburgh/ ; P50AG005142//University of Southern California/ ; P50AG005136//University of Washington/ ; P50AG033514//University of Wisconsin/ ; P20AG068082//Vanderbilt University/ ; P30AG072947//WakeForest/ ; P01AG03991//Washington University, St.Louis/ ; P01AG026276//Washington University, St.Louis/ ; P20MH071616//Washington University, St.Louis/ ; P30AG066444//Washington University, St.Louis/ ; P30NS098577//Washington University, St.Louis/ ; R01AG021910//Washington University, St.Louis/ ; R01AG043434//Washington University, St.Louis/ ; R01EB009352//Washington University, St.Louis/ ; UL1TR000448//Washington University, St.Louis/ ; U24RR021382//Washington University, St.Louis/ ; //Avid Radiopharmaceuticals/Eli Lilly/ ; P50AG047270//Yale/ ; R01AG052560//Yale/ ; R01AG062276//Yale/ ; P30AG066506-03//1Florida/ ; P50AG047266//1Florida/ ; //Key and Dominant Discipline Construction Project of the Health Commission of Guizhou Province in 2023, China/ ; 2021ZD0201801//STI2023-Major Projects/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/pathology/complications/psychology ; Male ; Female ; Aged ; *Depression/diagnostic imaging/pathology/etiology ; *Brain/pathology/diagnostic imaging ; Neuroimaging ; Magnetic Resonance Imaging ; Atrophy/pathology ; Aged, 80 and over ; Organ Size ; Hippocampus/pathology/diagnostic imaging ; Neuropsychological Tests ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) often co-occurs with depression, affecting cognitive function and quality of life. Understanding the neurobiological links between brain abnormalities and depressive symptoms is essential for effective treatment.

METHODS: We analyzed 2,722 participants from the National Alzheimer's Coordinating Center, including 886 AD patients and 1,836 cognitively normal controls. Neuroimaging assessed brain volumes, while depressive symptoms were measured using the Geriatric Depression Scale. Multiple linear regression and mediation analyses evaluated associations between brain structure, cognitive function, and depression.

RESULTS: AD patients had significantly higher rates of depressive symptoms (35.3% vs. 14.7%; p < 0.001) and cognitive impairments (mean Mini-Mental State Examination [MMSE]: 23.1 vs. 28.9; p < 0.001). Hippocampal atrophy mediated the relationship between depression and AD (indirect effect = -0.107; p < 0.001).

CONCLUSION: Hippocampal atrophy significantly mediates the relationship between depression and AD, suggesting targeted interventions may enhance patient outcomes.},
}

Humans
*Alzheimer Disease/diagnostic imaging/pathology/complications/psychology
Male
Female
Aged
*Depression/diagnostic imaging/pathology/etiology
*Brain/pathology/diagnostic imaging
Neuroimaging
Magnetic Resonance Imaging
Atrophy/pathology
Aged, 80 and over
Organ Size
Hippocampus/pathology/diagnostic imaging
Neuropsychological Tests

@article {pmid41611634,
year = {2026},
author = {Zhang, YC and Zhang, XT and Chen, PY and Zhou, ZY and Huang, MQ and He, KW},
title = {Impaired adrenergic regulation of Kv channels underlies LC hyperactivity and early-onset sleep disruption in AD-like amyloidogenic mice.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71127},
doi = {10.1002/alz.71127},
pmid = {41611634},
issn = {1552-5279},
support = {22ZR1475100//Shanghai Science and Technology Development Funds/ ; 32271004//NSFC/ ; 32070963//NSFC/ ; LG-ADB410101//Lingang Laboratory/ ; 2019SHZDZX02//Shanghai Municipal Science and Technology Major Project/ ; },
mesh = {Animals ; *Locus Coeruleus/physiopathology/drug effects/metabolism ; Mice ; Disease Models, Animal ; Mice, Transgenic ; *Alzheimer Disease/complications/metabolism ; *Sleep Wake Disorders/metabolism/etiology ; *Receptors, Adrenergic, alpha-2/metabolism ; Amyloid beta-Peptides/metabolism ; Guanfacine/pharmacology ; Neurons/drug effects ; Adrenergic alpha-2 Receptor Agonists/pharmacology ; *Potassium Channels, Voltage-Gated/metabolism ; Carbamates/pharmacology ; Phenylenediamines/pharmacology ; Male ; },
abstract = {INTRODUCTION: Sleep-wake disturbances frequently occur at early stages of Alzheimer's disease (AD) and accelerate disease progression, but the underlying neural mechanisms are not fully understood.

METHODS: We examined sleep-wake behavior and locus coeruleus (LC) activity in young 5xFAD mice using electrophysiology and pharmacological approaches targeting adrenergic signaling and potassium channels.

RESULTS: 5xFAD mice displayed dark phase-specific hyperarousal and impaired brain state transitions by 2 months of age. LC neurons exhibited increased tonic firing due to impaired Kv4 and Kv7 potassium channel conductance, resulting from soluble amyloid beta (Aβ)-induced disruption of α2A adrenergic receptor regulation. Pharmacological activation of α2A adrenergic receptors restored Kv4/7 function and normalized LC excitability. Local administration of guanfacine (α2A agonist) or retigabine (Kv7 modulator) significantly rescued sleep-wake disturbances.

DISCUSSION: These findings identify LC hyperexcitability as a mechanistic driver of early sleep disruption in AD and implicate α2A receptors and Kv7 channels as promising therapeutic targets for early intervention.},
}

Animals
*Locus Coeruleus/physiopathology/drug effects/metabolism
Mice
Disease Models, Animal
Mice, Transgenic
*Alzheimer Disease/complications/metabolism
*Sleep Wake Disorders/metabolism/etiology
*Receptors, Adrenergic, alpha-2/metabolism
Amyloid beta-Peptides/metabolism
Guanfacine/pharmacology
Neurons/drug effects
Adrenergic alpha-2 Receptor Agonists/pharmacology
*Potassium Channels, Voltage-Gated/metabolism
Carbamates/pharmacology
Phenylenediamines/pharmacology
Male

@article {pmid41611629,
year = {2026},
author = {Enduru, N and Zhao, Z},
title = {PRISM-xQTL: Pleiotropic Relationships Integrated with System-level Multiomic QTL analysis for causal genes and molecular mediators in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71073},
doi = {10.1002/alz.71073},
pmid = {41611629},
issn = {1552-5279},
support = {U01AG079847/NH/NIH HHS/United States ; R01LM012806/NH/NIH HHS/United States ; R21AG087299/NH/NIH HHS/United States ; CPRIT RP240610//Cancer Prevention and Research Institute of Texas/ ; //Ranajit Chakraborty, PhD Fellowship in Human Genetics/ ; },
mesh = {*Quantitative Trait Loci/genetics ; Humans ; *Alzheimer Disease/genetics ; Polymorphism, Single Nucleotide/genetics ; Genome-Wide Association Study ; *Genetic Pleiotropy/genetics ; Genetic Predisposition to Disease/genetics ; Mendelian Randomization Analysis ; Genotype ; },
abstract = {INTRODUCTION: Most Alzheimer's disease (AD) risk variants identified by genome-wide association studies (GWAS) reside in noncoding regions, complicating causal interpretation.

METHODS: We developed PRISM-xQTL (Pleiotropic Relationships Integrated with System-level Multiomic QTL), integrating pleiotropy, co-localization, Mendelian randomization, and mediation analyses across multiomic quantitative trait loci (QTLs; expression QTL [eQTL], methylation QTL [meQTL], splicing QTL [sQTL], proteomic [pQTL], single-cell [sc-eQTL]). Seventy pleiotropic single-nucleotide polymorphisms (SNPs) shared between AD and 11 immune disorders were analyzed. AlphaGenome assessed functional regulation, and The Alzheimer's Cell Atlas (TACA) database was used for drug-target relevance of FCER1G.

RESULTS: Across 54 Genotype-Tissue Expression (GTEx) tissues, 410 SNP-gene-tissue co-localizations were identified. SNP rs4233366 co-localized with eQTL/meQTL signals at FCER1G, whereas TSPAN14, ISYNA1, and ELL showed splicing and single-cell associations. Mendelian randomization and mediation analyses indicated cytosine-phosphate-Guanine (CpG) sites might effect on AD risk mediated through FCER1G. AlphaGenome and TACA validated FCER1G's the regulatory function and therapeutic relevance of FCER1G.

DISCUSSION: PRISM-xQTL refines causal inference for noncoding risk variants, highlighting immune regulatory mechanisms and prioritizing therapeutic targets in AD.

HIGHLIGHTS: We developed PRISM-xQTL (Pleiotropic Relationships Integrated with System-level Multiomic QTL), a multiomic framework integrating pleiotropy, co-localization, Mendelian randomization, and mediation analyses to dissect genetic regulation in Alzheimer's disease (AD) and immune-mediated diseases. Identified 410 single-nucleotide polymorphism (SNP)-gene-tissue co-localizations across 54 Genotype-Tissue Expression (GTEx) tissues, including 28 multi-gene/multi-tissue signals, 35 methylation quantitative trait locus (meQTL) pairs in blood, with rs4233366 and rs479486 overlapping expression QTLs (eQTLs). Multi-trait co-localization, Mendelian randomization and mediation analyses at rs4233366 and rs479486 revealed convergent regulatory effects across genes and tissues. AlphaGenome profiling showed that rs4233366 drives allele-specific transcriptional and splicing regulation at FCER1G, linking immune signaling to AD risk.},
}

*Quantitative Trait Loci/genetics
Humans
*Alzheimer Disease/genetics
Polymorphism, Single Nucleotide/genetics
Genome-Wide Association Study
*Genetic Pleiotropy/genetics
Genetic Predisposition to Disease/genetics
Mendelian Randomization Analysis
Genotype

@article {pmid41611624,
year = {2026},
author = {Donohue, MC and Hussen, K and Langford, O and Gallardo, R and Jimenez-Maggiora, G and Aisen, PS and , },
title = {Alzheimer's clinical research data via R packages: The alzverse.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {2},
pages = {e71152},
doi = {10.1002/alz.71152},
pmid = {41611624},
issn = {1552-5279},
support = {//Alzheimer's Disease Neuroimaging Initiative/ ; /AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; //Northern California Institute for Research and Education/ ; //ADNI/ ; /EB/NIBIB NIH HHS/United States ; /CAPMC/CIHR/Canada ; //Foundation for the National Institutes of Health/ ; //AbbVie/ ; //Alzheimer's Association; Alzheimer's Drug Discovery Foundation/ ; //Araclon Biotech/ ; //BioClinica, Inc./ ; //Biogen/ ; //BristolMyers Squibb Company/ ; //CereSpir, Inc./ ; //Eisai Inc./ ; //Elan Pharmaceuticals, Inc./ ; //Eli Lilly and Company/ ; //Genentech, Inc./ ; //Fujirebio/ ; //GE Healthcare/ ; //IXICO Ltd./ ; //Johnson & Johnson Pharmaceutical Research & Development LLC./ ; //Lumosity/ ; //Lundbeck/ ; //Merck & Co., Inc./ ; //Meso Scale Diagnostics, LLC./ ; //NeuroRx Research/ ; //Neurotrack Technologies/ ; //Novartis Pharmaceuticals Corporation/ ; //Pfizer Inc./ ; //Piramal Imaging/ ; //Servier/ ; //Takeda Pharmaceutical Company/ ; //Transition Therapeutics/ ; //NIA/ ; U19AG024904/GF/NIH HHS/United States ; U24AG057437/GF/NIH HHS/United States ; /NH/NIH HHS/United States ; //GHR Foundation/ ; //Davis Alzheimer Prevention Program/ ; //Yugilbar Foundation/ ; //Women's Hospital/ ; //Avid Radiopharmaceuticals/ ; //Cogstate/ ; //Albert Einstein College of Medicine and the Foundation for Neurologic Diseases/ ; //SCELC/ ; //Statewide California Electronic Library Consortium/ ; //Epstein Family Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging ; Reproducibility of Results ; *Biomedical Research ; Neuroimaging ; *Information Dissemination/methods ; Biomarkers ; },
abstract = {INTRODUCTION: Sharing clinical research data is essential for advancing Alzheimer's disease (AD) research, yet challenges in accessibility, standardization, documentation, usability, and reproducibility persist.

METHODS: We developed R data packages to streamline access to curated datasets from key AD studies. A4LEARN includes data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) randomized trial and its companion observational study, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN). ADNIMERGE2 contains curated data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a longitudinal biomarker and imaging study.

RESULTS: These packages bundle data, documentation, and reproducible analysis vignettes into portable, analysis-ready formats that can be installed and used within R. We also introduce the alzverse package, which applies a common data standard to integrate study-specific packages and facilitate meta-analyses.

DISCUSSION: By promoting collaboration, transparency, and reproducibility, R data packages provide a scalable framework to accelerate AD clinical research.

HIGHLIGHTS: R packages enable access to curated Alzheimer's clinical study datasets. A4LEARN and ADNIMERGE2 provide portable, analysis-ready data resources. R packages integrate data, documentation, and reproducible analysis vignettes. alzverse unifies study packages via common standards to support meta-analyses. Tools promote transparency, collaboration, and reproducibility in Alzheimer's disease (AD) research.},
}

Humans
*Alzheimer Disease/diagnostic imaging
Reproducibility of Results
*Biomedical Research
Neuroimaging
*Information Dissemination/methods
Biomarkers

@article {pmid41611541,
year = {2026},
author = {Gu, L and Qu, L and Zhao, Y and Yao, S},
title = {Development and Validation of a Machine Learning Model for Dementia Staging in a Heterogeneous Cognitive Impairment Cohort Using Multimodal Features.},
journal = {Academic radiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.acra.2026.01.009},
pmid = {41611541},
issn = {1878-4046},
abstract = {RATIONALE AND OBJECTIVES: With the emergence of disease-modifying therapies, precise staging of dementia is urgent. This study aimed to develop a machine learning model integrating multimodal data to achieve objective staging of dementia severity in patients with cognitive impairment.

MATERIALS AND METHODS: A total of 149 patients (100 with Alzheimer's disease) were recruited. Demographic data, neuropsychological scores, and multimodal PET features were collected. Subjects were randomly split (7:3) into training and validation cohorts. PET features were screened using Boruta and LASSO to generate composite SUVR scores, while key demographic and neuropsychological predictors were identified through univariate and multivariate logistic regression analyses. Seven machine learning algorithms (logistic regression, decision tree, random forest, XGBoost, LightGBM, support vector machine, and artificial neural network) were trained using grid search and fivefold cross-validation. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA), with SHAP analysis employed for interpretability.

RESULTS: The cohort comprised 80 very mild-to-mild (CDR 0.5-1) and 69 moderate-to-severe (CDR 2-3) dementia cases. Key predictors included years of education, MMSE, and composite amyloid and FDG SUVR scores. The XGBoost model demonstrated robust performance, achieving an AUC of 0.888 (95% CI: 0.777-0.967) in the independent validation cohort. SHAP analysis identified MMSE and composite FDG SUVR scores as the most significant contributors to disease staging.

CONCLUSION: This study constructed and internally validated an interpretable multimodal model for dementia severity staging. While the results are promising, the developed web-based tool currently serves as a proof-of-concept to demonstrate how such models could potentially assist in optimizing patient management and screening candidates for novel therapies, pending further external validation.},
}

@article {pmid41611469,
year = {2026},
author = {Joerg, M and Kristen, M and Walz, L and Lietz, C and Mueller, M and Nathal, S and Marchand, V and Motorin, Y and Winz, ML and Helm, M and Friedland, K},
title = {Complementary DNA oligonucleotide direct in-gel quantification (cDINGQ) for precise tRNA fragment analysis.},
journal = {RNA (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1261/rna.080749.125},
pmid = {41611469},
issn = {1469-9001},
abstract = {tRNA-derived fragments have emerged as critical regulators in various biological processes, but reliable methods for their quantification remain a challenge due to their small size and extensive RNA modifications. In this study, we present the newly developed Complementary DNA Oligonucleotide Direct In-Gel Quantification (cDINGQ) method for tRF analysis and compare it with traditional radioactive [[32]P] Northern blotting, non-radioactive approaches, and high-throughput Illumina sequencing under different experimental conditions. The cDINGQ method, utilizing Cy5-labeled hybridization probes, offers high specificity and sensitivity for detecting tRFs with significantly reduced processing time and costs. By applying these techniques to an Alzheimer's disease (AD) cell model, we demonstrate the reliability of these methods in detecting subtle variations in tRF abundance. Our findings highlight the sensitivity, specificity, and applicability of each method, addressing limitations such as RNA input requirements and probe hybridization conditions. The study further explores the utility of these methods for detecting tRFs in various biological contexts, emphasizing their potential for future research and biomarker discovery in disease-related studies.},
}

@article {pmid41611403,
year = {2026},
author = {Li, Y and He, Y and Zhang, W and Yang, M and Yu, W and Zhang, Z},
title = {Specific lysine guanidination and long alkyl chain tagging-assisted negative enrichment strategy enables comprehensive profiling of protein N-terminal acetylome.},
journal = {Analytica chimica acta},
volume = {1388},
number = {},
pages = {345112},
doi = {10.1016/j.aca.2026.345112},
pmid = {41611403},
issn = {1873-4324},
mesh = {Acetylation ; *Lysine/chemistry/metabolism ; Humans ; Animals ; HeLa Cells ; Mice ; *Peptides/chemistry/metabolism/analysis ; },
abstract = {BACKGROUND: Protein N-terminal acetylation (Nt-acetylation) is a widespread and essential modification in both eukaryotes and prokaryotes. To achieve in-depth profiling of Nt-acetylome, enrichment of Nt-acetylated peptides prior to mass spectrometry (MS) analysis is crucial, as their inherently low ionization efficiency is further suppressed in complex peptide mixtures. However, current methods are constrained by low enrichment selectivity and insufficient proteolytic digestion efficiency toward Nt-acetylated peptides.

RESULTS: Herein, we present a novel and effective enrichment method involving the specific blocking of lysine ε-amino groups by guanidination and long alkyl chain tagging to N-terminal/internal peptides with free α-amino groups. Due to their enhanced hydrophobicity, the alkylated N-terminal/internal peptides could be efficiently depleted via a C18 column, thus achieving the negative enrichment of Nt-acetylated peptides. Specific guanidination of lysine residues ensures high enrichment selectivity and efficient tryptic digestion of Nt-acetylated peptides. In a single-shot analysis of HeLa cells, our method yielded a significant 4-fold increase in the identification number of Nt-acetylated peptides compared to direct analysis. When coupled with high-pH C18 fractionation, this approach identified 4957 unique Nt-acetylated peptides, corresponding to 3042 acetylated N-termini and 902 putatively neo-acetylated N-termini, markedly expanding the identification coverage of current Nt-acetylation dataset. Furthermore, this method was successfully applied to the quantification of N-terminal acetylome in hippocampal tissues from Alzheimer's disease (AD) mice modeled by amyloid-beta (Aβ) hippocampal injection.

SIGNIFICANCE: Our method exhibits high enrichment selectivity, efficient proteolytic efficiency and minimal bias toward Nt-acetylated peptides in complex samples. This robust and versatile strategy offers an efficient alternative for comprehensive profiling of Nt-acetylome, thereby facilitating deeper insights into the physiological and pathological functions of Nt-acetylation across diverse biological systems.},
}

Acetylation
*Lysine/chemistry/metabolism
Humans
Animals
HeLa Cells
Mice
*Peptides/chemistry/metabolism/analysis

@article {pmid41611033,
year = {2026},
author = {Zeng, X and Peng, D and Shen, Y and Tang, L and Ran, T and Pan, Z and Liu, H},
title = {Bletilla striata polysaccharide alleviates Alzheimer's disease in Caenorhabditis elegans by modulating autophagy via the insulin/AMPK pathway.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.01.051},
pmid = {41611033},
issn = {1873-4596},
abstract = {Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the abnormal aggregation of amyloid-β (Aβ). Bletilla striata polysaccharide (BSP), the primary active component of the traditional Chinese medicine Bletilla striata, exhibits various pharmacological effects including hemostatic, antioxidant, anti-inflammatory, and immunomodulatory activities. This study aimed to systematically investigate the protective effects and molecular mechanisms of BSP in Caenorhabditis elegans AD model. We found that BSP effectively alleviated the paralysis phenotype in AD worms, with optimal efficacy observed at a concentration of 100 μg/mL. Furthermore, BSP significantly extended the lifespan of both wild type and AD worms, reduced lipofuscin deposition and egg-laying capacity, improved neuromuscular function, learning ability, and stress resistance, and lowered the level of oxidative stress in vivo. Additionally, BSP treatment markedly suppressed Aβ aggregation in AD worms.Transcriptomic analysis revealed that BSP significantly regulates the autophagy pathway. In combination with genetic experiments, we further elucidated that BSP coordinates the insulin and AMPK signaling pathways to modulate autophagy, thereby reducing abnormal autophagosome accumulation and restoring autophagic homeostasis. Notably, the neuroprotective effects of BSP were completely abolished in mutants of key insulin signaling pathway genes (daf-2, age-1, akt-1, akt-2, daf-16) and the AMPK homologous gene aak-2, indicating that its efficacy is associated with the insulin/AMPK-autophagy regulatory axis. This study reveals the mechanism by which BSP ameliorates AD pathology through multi-target and multi-pathway regulation of autophagy, providing a new theoretical basis for its development as a candidate therapeutic agent for AD and further highlighting the potential medical value of Bletilla striata in combating AD.},
}

@article {pmid41610905,
year = {2026},
author = {O'Toole, HJ and James, A and Nasim, N and Hadley, DJ and Hale, EJ and He, Q and Bein, KJ and Valenzuela, A and Rojalin, T and Dugger, BN and Wexler, AS and Lein, PJ and Carney, RP},
title = {Spatial and spectral mapping of traffic-related nanoparticles in hippocampal subregions of an Alzheimer disease model.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127730},
doi = {10.1016/j.envpol.2026.127730},
pmid = {41610905},
issn = {1873-6424},
abstract = {Chronic exposure to traffic-related air pollution (TRAP) is linked to increased risk of neurodegenerative diseases, including Alzheimer disease (AD). Ultrafine particulate matter (UFPM) is a suspected driver of TRAP neurotoxicity, but its spatial interactions with AD pathology remain poorly defined. We investigated the distribution, composition, and pathological context of TRAP-derived UFPM in the hippocampus of TgF344-AD rats chronically exposed to TRAP or filtered air (FA) for 14 months. Using a multimodal imaging workflow that combines enhanced darkfield hyperspectral imaging (EDF-HSI) with confocal immunofluorescence for microglia (CD68/Iba1) and amyloid beta (Aβ) plaques (Thioflavin S), we mapped the localization and spectral properties of UFPM in situ. UFPM accumulation was elevated in TRAP-exposed females, suggesting sex-specific vulnerability in blood-brain barrier permeability or particle accumulation. Particles near plaques showed red-shifted spectral signatures, suggestive of biochemical transformation. Dimension reduction revealed clustering of particle spectra by TRAP exposure and plaque proximity. However, UFPM was rarely found within plaques or microglia, implying indirect neuroimmune modulation. These findings highlight a novel spatial and spectral imaging approach for characterizing environmental nanoparticle interactions in the brain and suggests chronic TRAP exposure may influence AD-related inflammation and pathology in a sex- and region-dependent manner in this rodent model.},
}

@article {pmid41610849,
year = {2026},
author = {Samelson, AJ and Ariqat, N and McKetney, J and Rohanitazangi, G and Parra Bravo, C and Bose, RS and Travaglini, KJ and Lam, VL and Goodness, D and Ta, T and Dixon, G and Marzette, E and Jin, J and Tian, R and Tse, E and Abskharon, R and Pan, HS and Carroll, EC and Lawrence, RE and Gestwicki, JE and Rexach, JE and Eisenberg, DS and Kanaan, NM and Southworth, DR and Gross, JD and Gan, L and Swaney, DL and Kampmann, M},
title = {CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.12.038},
pmid = {41610849},
issn = {1097-4172},
abstract = {Aggregation of the protein tau defines tauopathies, the most common age-related neurodegenerative diseases, which include Alzheimer's disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation, dysfunction, and death. However, molecular mechanisms underlying cell-type-selective vulnerability are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPRi screen in induced pluripotent stem cell (iPSC)-derived neurons. The screen uncovered both known and unexpected pathways, including UFMylation and GPI anchor biosynthesis, which control tau oligomer levels. We discovered that the E3 ubiquitin ligase CRL5[SOCS4] controls tau levels in human neurons, ubiquitinates tau, and is correlated with resilience to tauopathies in human disease. Disruption of mitochondrial function promotes proteasomal misprocessing of tau, generating disease-relevant tau proteolytic fragments and changing tau aggregation in vitro. These results systematically reveal principles of tau proteostasis in human neurons and suggest potential therapeutic targets for tauopathies.},
}

@article {pmid41610783,
year = {2026},
author = {Turrisi, R and Patané, G},
title = {Generating synthetic MRI scans for improving Alzheimer's disease diagnosis.},
journal = {Medical image analysis},
volume = {110},
number = {},
pages = {103947},
doi = {10.1016/j.media.2026.103947},
pmid = {41610783},
issn = {1361-8423},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia. Magnetic Resonance Imaging (MRI) combined with Machine Learning (ML) enables early diagnosis, but ML models often underperform when trained on small, heterogeneous medical datasets. Transfer Learning (TL) helps mitigate this limitation, yet models pre-trained on 2D natural images still fall short of those trained directly on related 3D MRI data. To address this gap, we introduce an intermediate strategy based on synthetic data generation. Specifically, we propose a conditional Denoising Diffusion Probabilistic Model (DDPM) to synthesise 2D projections (axial, coronal, sagittal) of brain MRI scans across three clinical groups: Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and AD. A total of 9000 synthetic images are used for pre-training 2D models, which are subsequently extended to 3D via axial, coronal, and sagittal convolutions and fine-tuned on real-world small datasets. Our method achieves 91.3% accuracy in binary (CN vs. AD) and 74.5% in three-class (CN/MCI/AD) classification on the 3T ADNI dataset, outperforming both models trained from scratch and those pre-trained on ImageNet. Our 2D ADnet achieved state-of-the-art performance on OASIS-2 (59.3% accuracy, 57.6% F1), surpassing all competitor models and confirming the robustness of synthetic data pre-training. These results show synthetic diffusion-based pre-training as a promising bridge between natural image TL and medical MRI data.},
}

@article {pmid41610745,
year = {2026},
author = {Zhao, J and Yang, G and Ruan, Y and Yuan, R and Chen, S},
title = {Single-atom co anchored UiO-66 to boost electrochemiluminescence of MoS2 for bioanalysis.},
journal = {Biosensors & bioelectronics},
volume = {299},
number = {},
pages = {118432},
doi = {10.1016/j.bios.2026.118432},
pmid = {41610745},
issn = {1873-4235},
abstract = {Single-atom catalysts (SACs) hold significant promise for improving the electrochemiluminescence (ECL) efficiency. However, the preparation of SACs reported in the ECL field usually relies on carbon-nitrogen-based materials as substrates and requires high-temperature pyrolysis (>800 °C), suffering from the limitation in the anchoring materials and the deficiency of insufficient active site density caused by high-temperature calcination. This work developed zirconium-based metal-organic framework UiO-66 as the carrier to successively anchor the Co single-atom (CoSA) and the ECL emitter MoS2 under mild conditions (not exceeding 200 °C). CoSA not only can optimize the electronic structure of MoS2 to effectively promote the formation of Co(IV)=O, but also can act as the co-reactant accelerator to efficiently catalyze the reduction of coreactant S2O8[2-]. Meanwhile, the Mo-O-Zr bimetallic sites formed between UiO-66 and MoS2 can enhance the charge carrier mobility within MoS2. As a result, the ECL emission of MoS2 at -1.6 V was remarkably boosted when using step pulse as the electrochemical method. The synthesized MoS2@CoSA/UiO-66 composite integrated an aptamer recognition-driven cascaded polymerase amplification to achieve ultrasensitive ECL detection of p-Tau as crucial biomarker for Alzheimer's disease (AD). CoSA/UiO-66 exhibits broad application prospects in improving ECL efficiency. MoS2@CoSA/UiO-66 builds a highly sensitive ECL sensing platform for detecting the biomarkers of AD and other diseases.},
}

@article {pmid41610733,
year = {2026},
author = {Young, VM and Zeynoun, J and Ruiz Laza, A and Salardini, A and Frei, CR and Gaspard, C and Kautz, T and Macedo E Cordeiro, T and Pase, MP and Gelfond, J and Himali, JJ and Teixeira, AL and Seshadri, S and Baril, AA},
title = {Association between sleep duration and fluid biomarkers of Alzheimer's disease: A systematic review.},
journal = {Sleep medicine reviews},
volume = {86},
number = {},
pages = {102242},
doi = {10.1016/j.smrv.2026.102242},
pmid = {41610733},
issn = {1532-2955},
abstract = {This systematic review (PROSPERO CRD420246206360) investigated relationships between self-reported or objective sleep duration and fluid biomarkers of Alzheimer's disease pathology and neurodegeneration: cerebrospinal fluid or blood Aβ, p-tau181, t-tau, NfL and GFAP. We searched PubMed, SCOPUS, and CINAHL from inception to September 2024. Twenty studies (n = 12,445) met inclusion criteria (13 cerebrospinal fluid biomarkers [n = 2836]; 7 blood biomarkers [n = 9609]). Study quality was assessed using Newcastle-Ottawa scales. Whereas many studies did not report any associations, some trends emerged: short sleep duration was associated with higher cerebrospinal fluid t-tau and p-tau181 and lower cerebrospinal fluid or blood Aβ42 across multiple studies. Longer sleep duration showed more variable associations, with some suggesting either worse or better biomarker profiles (e.g., higher and lower fluid t-tau, p-tau181, or Aβ42). Two studies investigating non-linear relationships identified U-shaped associations, suggesting both short (≤5-6 h) and long (≥8 h) sleep durations are associated with altered biomarker profiles. The predominantly cross-sectional and high heterogeneity of the available evidence, as well as the relatively small number of studies by individual biomarker (especially for NfL and GFAP) limit conclusions about sleep-biomarker relationships. Future research should investigate emerging blood-based biomarkers and explore temporal associations between sleep duration and Alzheimer's disease biomarker changes.},
}

@article {pmid41610695,
year = {2026},
author = {Yan, Y and Chen, Y and Yang, F and Zhao, R and Tian, D and Deng, L and Xie, M},
title = {In-situ engineering of a covalent organic framework-based biomimetic nanoplatform for multi-target therapy of Alzheimer's disease.},
journal = {Biomaterials advances},
volume = {182},
number = {},
pages = {214728},
doi = {10.1016/j.bioadv.2026.214728},
pmid = {41610695},
issn = {2772-9508},
abstract = {To address the complex pathology of Alzheimer's disease (AD), including abnormal amyloid-β (Aβ) aggregation, metal ion homeostasis disruption and oxidative stress, we developed an integrated multifunctional nanoplatform. This platform leveraged a covalent organic framework (TD-COF) with intrinsic capabilities for Cu[2+] chelation and Aβ inhibition as the carrier. Through in-situ engineering, ultrafine palladium nanoparticles (PdNPs) were anchored to construct a stable, functionally integrated core (Pd-COF). However, due to limitations of nanomaterials such as short half-life and poor brain targeting, we further employed red blood cell (RBC) membrane for biomimetic modification, yielding the final platform Pd-COF-RBC. In vitro experiments demonstrated that Pd-COF-RBC concurrently achieved Cu[2+] chelation, Aβ fibrillation inhibition and reactive oxygen species (ROS) scavenging. Notably, the design of Pd-COF also regulated the size and dispersibility of PdNPs, enhancing catalase-like (CAT) activity by 34.7%. In Aβ-induced cellular models, the material effectively alleviated oxidative stress and mitochondrial dysfunction, increasing cell survival by over 78.4%. Further experiments confirmed that Pd-COF-RBC modified with RBC membrane possessed good biocompatibility, long circulation property and brain accumulation capacity. Based on these findings, we evaluated its therapeutic potential in the transgenic AD C. elegans model. The results demonstrated the motor and cognitive functions of the worms were markedly restored, with the average paralysis time prolonged by approximately 37.3% and the chemotactic index recovering to near wild-type levels. Thus, the study has promise for providing experimental evidence for multi-target intervention against the complex pathological network of AD via an integrated strategy of in situ engineering and biomimetic modification.},
}

@article {pmid41610685,
year = {2026},
author = {Gómez-Morales, A and Bahrami, R},
title = {Unseen support: The needs of Alzheimer's disease and related dementias' secondary family caregivers and a way forward.},
journal = {Geriatric nursing (New York, N.Y.)},
volume = {69},
number = {},
pages = {103911},
doi = {10.1016/j.gerinurse.2026.103911},
pmid = {41610685},
issn = {1528-3984},
abstract = {OBJECTIVES: This study aimed to better understand and identify the needs of secondary caregivers of individuals with memory challenges and explore their role in supporting primary caregivers to inform the development of a tailored intervention for secondary caregivers of people with Alzheimer's disease and related dementias.

METHODS: A complementary, sequential mixed-methods approach was used to achieve the goal. Phase one included an online survey with primary caregivers (N = 10) exploring how secondary caregivers support them and training opportunities. Phase two involved virtual focus groups with secondary caregivers (N = 13) with a semi-immersive virtual reality experience where participants embodied a person with dementia, and discussed their caregiving roles, challenges, and needs.

RESULTS: Primary caregivers identified secondary caregivers as helpful in reducing burden and stress. However, tensions existed due to unclear roles. Secondary caregivers reported emotional challenges and unclear role expectations. Virtual reality was valuable for increasing empathy. Both groups prioritized education in communication and managing challenging behaviors.

CONCLUSIONS: Semi-immersive virtual reality can help prepare secondary caregivers to support primary caregivers and their care recipients in key caregiving skills, while increasing dementia awareness and empathy.

CLINICAL IMPLICATIONS: Tailored interventions incorporating virtual reality may assist secondary caregivers in promoting positive health care outcomes and continuity of care for people with dementia and their primary caregivers.},
}

@article {pmid41610651,
year = {2026},
author = {Yang, F and Chen, Y and Yan, Y and Zhao, R and Deng, L and Tian, D and Xie, M},
title = {Biomimetic red blood cell membrane-coated cerium metal-organic framework for multi-target synergistic therapy of Alzheimer's disease.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {262},
number = {},
pages = {115464},
doi = {10.1016/j.colsurfb.2026.115464},
pmid = {41610651},
issn = {1873-4367},
abstract = {Pathological events in Alzheimer's disease (AD) typically involve β-amyloid (Aβ) plaque deposition, metal ion dysregulation, oxidative stress elevation, and chronic neuroinflammation, making single-target therapies unsatisfactory. Here, we first report a biomimetic nanoplatform based on red blood cell membrane-coated cerium metal-organic frameworks (Ce-MOF-RBC) that enables multi-target synergistic intervention against AD. The Ce-MOF core exhibits potent antioxidant activity, efficiently scavenging reactive oxygen species (ROS) and restoring mitochondrial membrane potential, while its carboxylate ligands chelate Cu[2 +] with high efficiency (49.26 %) to inhibit Cu[2+]-induced Aβ fibrillation and disassemble preformed fibrils. Ce-MOF-RBC further modulates microglial phenotype, enhancing Aβ phagocytosis and reducing neuroinflammation. Importantly, RBC membrane functionalization markedly improves biological performance by prolonging systemic circulation, enhancing blood-brain barrier (BBB) penetration, and leveraging its intrinsic affinity for Aβ peptides to enrich Aβ. In vivo fluorescence imaging and brain cryosections showed that Ce-MOF-RBC achieved robust accumulation in the cortex and hippocampus, with brain fluorescence intensities 27.33-fold higher than free DiD. In the C. elegans AD model, Ce-MOF-RBC reduced Aβ plaque fluorescence by 32.54 %, lowered ROS levels by 45.72 %, improved chemotaxis performance (chemotaxis index increased from 34.24 % to 68.34 %), and delayed paralysis onset from 10 h to 15 h, demonstrating significant rescue of cognitive and motor deficits. In summary, these findings highlight the first demonstration of a small-sized, biomimetic Ce-MOF-RBC nanoplatform that integrates antioxidant, metal-chelating, anti-aggregation, and immunomodulatory functions, offering a promising strategy for comprehensive AD therapy.},
}

@article {pmid41610646,
year = {2026},
author = {Kumar, S and Srivastava, S and Tan, CS and Abohashrh, M and Malviya, R},
title = {Correlation between oral disease and neurodegenerative disorders: Role of biological proteins for the modulation of oral-brain axis and gut-brain axis.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {262},
number = {},
pages = {115480},
doi = {10.1016/j.colsurfb.2026.115480},
pmid = {41610646},
issn = {1873-4367},
abstract = {Biological proteins play a crucial role at the intersection of oral health and neuroscience, offering promising opportunities for improved diagnosis, prevention, and treatment. This review highlights the molecular, inflammatory, and biochemical pathways linking oral diseases, particularly periodontal disease and microbial dysbiosis, with neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Key inflammatory, neuroprotective, and tissue-repair proteins play a crucial role in maintaining both oral integrity and neural function. Advances in proteomics and molecular imaging have clarified how protein misfolding, aggregation, and immune responses drive neuroinflammation and cognitive decline. Emerging therapies include protein-based biomaterials, such as hydrogels, nanocarriers, and protein-polymer hybrids, for delivering neuroprotective and regenerative agents through oral and nasal routes. Early diagnosis is being transformed by salivary proteomics and transcriptomics, enabling non-invasive detection of neurodegenerative biomarkers. Host-defense peptides and antimicrobial proteins also show promise in controlling oral infections that may exacerbate brain inflammation. Integrating oral biology, biomaterials science, and neuroscience is accelerating clinical translation through the development of innovative scaffolds and smart delivery systems. Despite challenges in biomarker validation and clinical application, advances in artificial intelligence, bioinformatics, and protein engineering are driving the future of personalized regenerative and preventive medicine. Overall, biological proteins provide a critical molecular link between oral and neural health, paving the way for novel non-invasive diagnostic and therapeutic strategies.},
}

@article {pmid41610520,
year = {2026},
author = {Preet Kaur, B and Sahoo, S and Chaurasia, R and Bhattacharyya, A and Sharma, AK and Mukherjee, M and Chakraborty, G},
title = {Advances in design and application of molecularly imprinted polymers for selective brain protein recognition in neurology.},
journal = {Biomedical materials (Bristol, England)},
volume = {},
number = {},
pages = {},
doi = {10.1088/1748-605X/ae3f6e},
pmid = {41610520},
issn = {1748-605X},
abstract = {Neurological diseases affect billions of people worldwide, including an array of infections, strokes, cancers, and neurodegenerative disorders like Alzheimer's and Parkinson's, which have seen rising mortality rates in recent decades. The blood-brain barrier (BBB) is a critical protective layer composed of tightly sealed endothelial cells that restrict the entry of most molecules into the brain. Typically, only small, lipophilic molecules can cross the BBB, while larger or hydrophilic drugs face significant delivery challenges. Molecularly imprinted polymers (MIPs) are synthetic materials designed to recognize specific molecules, creating 'molecular memory' for selective binding and release. MIPs offer benefits such as high stability, biocompatibility, sustained drug release, and cost-effectiveness, making them promise for drug delivery and biosensing applications. This review explores the potential of MIPs for targeting receptors on the BBB to improve selective drug delivery to the brain, highlighting design strategies and receptor targets critical for internalization.},
}

@article {pmid41610380,
year = {2026},
author = {Kivisäkk, P and Fatima, H and Wu, CY and Padmanabhan, N and Romero, D and Gorham, T and Weik, M and Dodge, HH and Scherzer, CR and Das, S and Chibnik, LB and Blacker, DL and Gomez-Isla, T and Oakley, DH and Frosch, MP and Hyman, BT and Demos, C and Sigal, G and Wohlstadter, JN and Serrano-Pozo, A and Arnold, SE},
title = {Postmortem Associations Between Alzheimer Disease Pathology and Plasma pTau217, GFAP, and NfL in AD and AD-Related Dementias.},
journal = {Neurology},
volume = {106},
number = {4},
pages = {e214351},
doi = {10.1212/WNL.0000000000214351},
pmid = {41610380},
issn = {1526-632X},
mesh = {Humans ; *Alzheimer Disease/pathology/blood ; Female ; *Neurofilament Proteins/blood ; Male ; Aged ; *Glial Fibrillary Acidic Protein/blood ; Biomarkers/blood ; *tau Proteins/blood ; Aged, 80 and over ; Longitudinal Studies ; Autopsy ; Brain/pathology ; Cross-Sectional Studies ; Cohort Studies ; },
abstract = {BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) and its related disorders (ADRDs) are characterized by a high frequency of copathologies. We aimed to determine the specificity of plasma pTau217, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) for AD neuropathological change (ADNC) in the presence of common ADRD copathologies.

METHODS: pTau217, GFAP, and NfL were measured using S-PLEX immunoassays from Meso Scale Discovery in banked plasma samples from 2 groups of participants in the Massachusetts Alzheimer's Disease Research Center (MADRC) Longitudinal Cohort study: (1) participants spanning the cognitive spectrum, who underwent brain autopsy, and blood collection within 6 years before death, and (2) participants with normal cognition and no neurologic diagnosis during 5 years of follow-up, but no autopsy data (normal controls [NCs]). Cross-sectional associations between biomarker levels and ADNC, primary neuropathologic diagnosis (NPDx1), and presence of non-AD copathologies were evaluated using linear regression models controlling for age, sex, and time to death.

RESULTS: One hundred eighty-seven participants with brain autopsy (NPDx1: AD n = 85; other n = 102; mean age: 74.3 years, 38.5% female; interval blood collection-death [mean ± SD]: 2.8 ± 1.6 years) and 67 NC without brain autopsy (mean age: 66.5 years, 71.6% female) were included. pTau217, but not GFAP, levels increased stepwise with increasing Thal phases (β = 0.61; 95% CI [0.24-0.97] to β = 0.91 [0.55-1.27]) and Braak stages (β = 0.59; [0.16-1.01] to β = 0.74 [0.33-1.15]). Although 23% of individuals with a non-AD NPDx1 had increased pTau217 levels using a cutoff defined by the contrast between ADNC and NC, the majority (62%) had intermediate/high ADNC copathology and the remaining pTau217+ individuals had borderline increased levels. By contrast, 48% of individuals without ADNC had increased GFAP levels. pTau217 and GFAP were not different in the presence or absence of cerebral amyloid angiopathy, α-synuclein or TDP-43 proteinopathies, or primary tauopathies. NfL was not specifically associated with ADNC.

DISCUSSION: Plasma pTau217, but not GFAP or NfL, levels accurately reflect the presence of ADNC in the brain even in individuals with an NPDx1 of a non-AD dementia. Thus, a positive plasma pTau217 test in an individual with a suspected non-AD dementia should not necessarily be considered a misdiagnosis of the presumed non-AD dementia or as a false positive, but rather as evidence of ADNC copathology.},
}

Humans
*Alzheimer Disease/pathology/blood
Female
*Neurofilament Proteins/blood
Male
Aged
*Glial Fibrillary Acidic Protein/blood
Biomarkers/blood
*tau Proteins/blood
Aged, 80 and over
Longitudinal Studies
Autopsy
Brain/pathology
Cross-Sectional Studies
Cohort Studies

@article {pmid41610377,
year = {2026},
author = {Irwin, DJ},
title = {Blood-Based Biomarkers and the Complexity of Neuropathologic Substrates of Alzheimer Disease and Related Disorders.},
journal = {Neurology},
volume = {106},
number = {4},
pages = {e214504},
doi = {10.1212/WNL.0000000000214504},
pmid = {41610377},
issn = {1526-632X},
}

@article {pmid41610326,
year = {2026},
author = {Guo, W and Cheng, Y and Yin, H and Li, S and Wan, Y and Li, C and Jiang, C and Zhou, J and Yuan, X and Wang, J},
title = {CRISPR-AD: Combinational Detection of Blood Protein and miRNA with Digital CRISPR-Based Assay Enable to Improve the Diagnostic Performance of Alzheimer's Disease.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c06080},
pmid = {41610326},
issn = {1520-6882},
abstract = {Blood-based biomarkers present a noninvasive approach for detecting and assessing Alzheimer's disease (AD) pathophysiology, always by using sophisticated instrumentation for accurate detection. Here, we introduce CRISPR-AD, a CRISPR/Cas-based digital assay designed for the combined detection of protein and microRNA in blood. This method achieves a limit of detection (LOD) as low as 60 fg/mL for phosphorylated tau217 (p-tau217) and 0.5 fM for microRNA-34a-5p (miRNA34a), enabling successful detection in both AD patients and healthy individuals. We find that the combined use of these biomarkers improves the ability to distinguish between AD patients and healthy participants, particularly in individuals with mild cognitive impairment (MCI). Additionally, we have developed a portable device that integrates a smartphone as an imaging system for point-of-care testing (POCT), offering the potential for early stage AD screening. This study represents the first effort to evaluate the combined detection of blood protein and microRNA biomarkers for AD, underscoring the potential of multiple biomarker combinations for more accurate AD diagnosis.},
}

@article {pmid41610056,
year = {2026},
author = {Kim, D and Lee, WJ and Jeon, DH and Cho, K},
title = {Education-Adjusted Interpretation of MMSE for Diagnostic Validity of Cognitive Disorders.},
journal = {Dementia and geriatric cognitive disorders},
volume = {},
number = {},
pages = {1-19},
doi = {10.1159/000550745},
pmid = {41610056},
issn = {1421-9824},
abstract = {Introduction The Mini-Mental State Examination (MMSE) is widely utilized in clinical settings for cognitive screening, yet its diagnostic accuracy is often influenced by demographic factors such as educational attainment. This study investigates the educational gradient in MMSE performance and evaluates whether uniform cutoff scores adequately distinguish cognitively normal (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD) patients across different educational strata. Methods A total of 300 older adults (CN = 100; MCI = 100; AD = 100) were retrospectively recruited from the Severance Hospital memory clinic, intentionally balanced to ensure statistical power and avoid class-imbalance bias across diagnostic groups. All participants completed the Korean version of MMSE and the Seoul Neuropsychological Screening Battery-II (SNSB-II) and underwent 3T brain MRI for hippocampal volumetry. Education level was categorized as low (≤6 years), medium (7-12 years), and high (≥13 years). MMSE diagnostic accuracy was evaluated using ROC curve analyses stratified by education. Interaction effects were tested via multiple linear regression, and correlations with hippocampal volume were assessed. Results MMSE scores showed a significant educational gradient, with higher education associated with higher performance (p < 0.001). MMSE scores demonstrated a pronounced educational gradient, with particularly reduced performance in individuals with low educational attainment, suggesting potential overestimation of cognitive impairment when uniform MMSE cutoffs are applied. ROC analyses revealed only moderate diagnostic accuracy of MMSE in the higher education groups (AUC = 0.83 and 0.78). The AUC was 0.73 (95% CI 0.58-0.88) in the low-education group; the AUC was 0.83 (95% CI 0.75-0.91) in the middle-education group; and 0.78 (95% CI 0.70-0.87) in the high-education group, suggesting only moderate diagnostic accuracy of MMSE. Conversely, lower education groups showed underperformance potentially unrelated to pathology. Regression models confirmed that education and diagnosis had additive but non-interacting effects on MMSE scores. MMSE correlated strongly with hippocampal volume (r = 0.739, p < 0.001), validating its general neuroanatomical relevance. Conclusion MMSE performance is substantially modulated by education, with uniform cutoffs yielding differential diagnostic validity across educational strata. We suggest education-adjusted interpretation of MMSE and emphasize the need for integrative diagnostic approaches combining cognitive testing with neuroimaging biomarkers.},
}

@article {pmid41609875,
year = {2026},
author = {Shahabinejad, E and Shakoeizadeh, A and Karimabad, MN and Asadi, F and Heydari, M and Salandari-Rabori, M},
title = {Utilizing nanotechnology to diagnose and treat central nervous system disorders.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {2},
pages = {209},
pmid = {41609875},
issn = {1590-3478},
mesh = {Humans ; *Central Nervous System Diseases/diagnosis/therapy/drug therapy ; *Nanotechnology/methods ; Animals ; *Drug Delivery Systems/methods ; Blood-Brain Barrier ; },
abstract = {The CNS presents a unique challenge to therapeutic intervention due to its sophisticated organization, the protective blood-brain barrier (BBB), and the low regenerative potential of neural tissue. Over the last few decades, nanotechnology has emerged as a revolutionary technology capable of transforming the diagnosis and treatment of CNS diseases, thereby offering new hope to patients with previously incurable neurodegenerative diseases. This review highlights the therapeutic and diagnostic potential of newer types of nanomaterials-i.e., nanoliposomes (NLs), metallic nanoparticles (MNPs), and carbon nanotubes (CNTs)-which have been found to cross the blood-brain barrier (BBB) and deliver drugs with enhanced specificity and efficacy. Nanoparticle-based therapies have revolutionized drug delivery, gene therapy, in vivo imaging, and molecular profiling for CNS diseases. However, despite such advancements, hurdles remain, particularly in terms of biocompatibility, long-term safety, and site-specific activity within complex biological systems. Herein, we summarize recent advances in the construction of smart nanocarriers and multi-functional platforms for overcoming physiological and pharmacological challenges in CNS therapy. Finally, we emphasize the urgent need for interdisciplinary studies to unlock the full clinical potential of nanotechnology in neurology and answer outstanding questions regarding toxicity, immune responses, and scalability for human application.},
}

Humans
*Central Nervous System Diseases/diagnosis/therapy/drug therapy
*Nanotechnology/methods
Animals
*Drug Delivery Systems/methods
Blood-Brain Barrier

@article {pmid41609827,
year = {2026},
author = {Parihar, M and Chen, Y and Xu, B and Bekena, S and Singh, RK and Zhu, Y and Trani, JF and Lee, JM and Carr, DB and Phuah, CL and Babulal, GM and , },
title = {White Matter Hyperintensity Burden and Decline in Driving Performance Among Older Adults.},
journal = {JAMA network open},
volume = {9},
number = {1},
pages = {e2554501},
doi = {10.1001/jamanetworkopen.2025.54501},
pmid = {41609827},
issn = {2574-3805},
mesh = {Humans ; Aged ; Male ; Female ; *Automobile Driving/statistics & numerical data ; *White Matter/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Longitudinal Studies ; Prospective Studies ; *Cognitive Dysfunction ; Aged, 80 and over ; Risk Factors ; Independent Living ; Antihypertensive Agents/therapeutic use ; },
abstract = {IMPORTANCE: White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.

OBJECTIVE: To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.

This prospective longitudinal cohort study enrolled community-dwelling older adults (≥65 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected from January 1, 2015, to December 31, 2024 (mean [SD] follow-up, 5.6 [1.8] years), with annual cognitive and clinical assessments.

EXPOSURE: Total and regional WMH volumes, cognitive status change, and antihypertensive medication use.

MAIN OUTCOMES AND MEASURES: Monthly driving trip frequency, trip distance, unique destinations, driving entropy, and safety events. Longitudinal associations were evaluated using linear mixed-effects models adjusted for demographic characteristics, socioeconomic status, and vascular risk.

RESULTS: Among 220 participants (mean [SD] age, 72.9 [5.0] years; 119 men [54%]) with low vascular risk (mean [SD] Framingham Stroke Risk Profile, 6.4% [1.3%]), greater baseline WMH burden was correlated with lower driving frequency (β = -0.16; 95% CI, -0.27 to -0.06; P = .002), reduced driving entropy (β = -0.17; 95% CI, -0.27 to -0.06; P = .002), and fewer unique destinations (β = -0.17; 95% CI, -0.27 to -0.07; P = .001). Longitudinally, higher WMH was associated with faster declines in driving frequency (β = -0.08; 95% CI, -0.13 to -0.04; P < .001), entropy (β = -0.11; 95% CI, -0.17 to -0.06; P < .001), and unique destinations (β = -0.09; 95% CI, -0.14 to -0.04; P < .001). Growth in posterior WMH burden showed the strongest association with increased crash risk (β = 1.71; 95% CI, 1.17-2.24; P < .001) among those developing cognitive impairment (38 [17%]). Among participants, 135 used antihypertensive therapy and 113 underwent follow-up MRI. Antihypertensive therapy, particularly angiotensin-converting enzyme inhibitors, was associated with attenuated WMH-related risky driving before adjustment, but not after adjustment (β = -0.17; 95% CI, -0.37 to 0.03; unadjusted P = .02; false discovery rate-adjusted P = .08). Sensitivity analyses confirmed associations were independent of Alzheimer dementia pathology.

CONCLUSIONS AND RELEVANCE: In this cohort study of older drivers, higher WMH burden, especially in posterior regions, was associated with progressive driving self-regulation and increased errors in those developing cognitive impairment. Antihypertensive use attenuated WMH-associated unsafe driving. Posterior WMH may represent a biomarker for identifying older drivers at risk and may inform mobility-preserving interventions in aging populations.},
}

Humans
Aged
Male
Female
*Automobile Driving/statistics & numerical data
*White Matter/diagnostic imaging/pathology
Magnetic Resonance Imaging
Longitudinal Studies
Prospective Studies
*Cognitive Dysfunction
Aged, 80 and over
Risk Factors
Independent Living
Antihypertensive Agents/therapeutic use

@article {pmid41609790,
year = {2026},
author = {Haußmann, A},
title = {[New treatments for Alzheimer disease : A challenge for radiology].},
journal = {Radiologie (Heidelberg, Germany)},
volume = {},
number = {},
pages = {},
pmid = {41609790},
issn = {2731-7056},
abstract = {Alzheimer's disease is one of the most common causes of dementia in older adults. Since 2024, monoclonal antibody therapy has been available, which can slow disease progression at certain stages. During therapy, magnetic resonance imaging changes called amyloid-related imaging abnormalities (ARIA)-edema (ARIA-E) and hemorrhage (ARIA-H)-must be monitored at specific points during treatment; depending on severity, therapy may need to be paused. Cerebral amyloid angiopathy (CAA) and its inflammatory form (CAA-I) should be considered in the differential diagnosis.},
}

@article {pmid41609580,
year = {2026},
author = {Purvinsh, Y and Matveyenka, M and Kurouski, D},
title = {Elucidation of Molecular Mechanisms of Lipid-Altered Cytotoxicity of TDP-43 Fibrils.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00934},
pmid = {41609580},
issn = {1948-7193},
abstract = {Progressive aggregation of TAR DNA-binding protein 43 (TDP-43) is a hallmark of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's disease, and limbic predominant age-related TDP-43 encephalopathy (LATE). This highly conserved nuclear RNA/DNA-binding protein is involved in the regulation of RNA processing. The C-terminal domain (CTD) of TDP-43 plays a key role in protein solubility, cellular localization, and protein-protein interactions. CTD is rich in glycine, glutamine, and asparagine, which facilitate TDP-43 aggregation into amyloid oligomers and fibrils observed in the brain. In this study, we examine the role of lipid bilayers in the aggregation properties of the CTD of TDP-43. We found that lipid bilayers composed of anionic phosphatidylserine and cardiolipin accelerated TDP-43 aggregation. Although lipids did not alter the secondary structure, they altered the cytotoxicity that TDP-43 fibrils exerted to rat dopaminergic cells. Using molecular methods, we showed that TDP-43 fibrils damage cell endosomes. This causes aggregate leakage into the cytosol, where TDP-43 fibrils impair cell autophagy, simultaneously triggering a severe unfolded protein response in the endoplasmic reticulum. Our results indicate that TDP-43 aggregation may be linked to pathological changes in the lipid profiles of neurons.},
}

@article {pmid41609364,
year = {2026},
author = {Ocal, D and Day, BL and Peters, A and Bancroft, M and Cash, D and Kaski, D and Ryan, NS and Crutch, SJ and Yong, KXX},
title = {Visual modulation of vestibular-evoked balance response disturbed by posterior cortical atrophy.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP290227},
pmid = {41609364},
issn = {1469-7793},
}

@article {pmid41609117,
year = {2026},
author = {Wu, CK and Dailey, JM and Donahue, JE},
title = {Behavioral Variant in Alzheimer's Disease.},
journal = {Acta neurologica Taiwanica},
volume = {35},
number = {1},
pages = {14-24},
doi = {10.4103/ant.ANT-D-25-00098},
pmid = {41609117},
issn = {1028-768X},
mesh = {Humans ; *Alzheimer Disease/psychology/diagnosis/complications ; Aged ; Male ; Female ; },
abstract = {In this review, the authors report on the development and discovery of atypical variants in Alzheimer's disease (AD). The behavioral variant of AD is emphasized and described in detail, in addition to its comparison with other variants. Furthermore, the newly developed diagnostic criteria and diagnostic approach are explained and applied for clinical practice in neurology. Principles of management and treatment for behavioral variants are highlighted. Three cases are reported to illustrate different courses of pathophysiology in behavioral variants in AD.},
}

Humans
*Alzheimer Disease/psychology/diagnosis/complications
Aged
Male
Female

@article {pmid41609047,
year = {2026},
author = {Wang, B and Shao, Y and Liang, R},
title = {Exercise Suppresses Insulin Resistance: A Potential Mechanism for Improving the Interaction Between Type 2 Diabetes and Alzheimer's Disease.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {1},
pages = {44389},
doi = {10.31083/JIN44389},
pmid = {41609047},
issn = {0219-6352},
support = {2023AFB978//Natural Science Foundation of Hubei Province of China/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/therapy ; *Insulin Resistance/physiology ; *Diabetes Mellitus, Type 2/metabolism/therapy ; Animals ; *Exercise/physiology ; *Exercise Therapy ; },
abstract = {Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, hyperinsulinemia, and impaired insulin sensitivity. Although classified as a metabolic disorder, T2DM also contributes to cognitive decline. Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. T2DM is strongly associated with AD and is considered a major risk factor for its development. AD is therefore recognized as a metabolic disorder mediated by cerebral insulin resistance, often termed "type 3 diabetes". T2DM and AD exhibit crosstalk, sharing overlapping molecular mechanisms including insulin resistance, mitochondrial dysfunction, oxidative stress, chronic inflammation, autophagy dysregulation, tau hyperphosphorylation, and β-amyloid deposition. Among these, insulin resistance may play a potential role in this interplay. As a non-pharmacological intervention, exercise demonstrates distinct advantages in preventing and managing metabolic and neurological disorders. Exercise maintains glucose homeostasis by mitigating insulin resistance, enhances insulin sensitivity, and concurrently reduces tau hyperphosphorylation and β-amyloid aggregation, thereby improving cognitive function. Building on current literature, this review explores how exercise mitigates insulin resistance to prevent and manage both T2DM and AD. It further proposes that insulin resistance may serve as a potential mechanistic link through which exercise modulates the pathological crosstalk between the two disorders.},
}

Humans
*Alzheimer Disease/metabolism/therapy
*Insulin Resistance/physiology
*Diabetes Mellitus, Type 2/metabolism/therapy
Animals
*Exercise/physiology
*Exercise Therapy

@article {pmid41609044,
year = {2026},
author = {Anschuetz, A and Listyono, R and Vorley, T and Platt, B and Harrington, CR and Riedel, G and Schwab, K},
title = {The Icelandic Mutation in the Murine APP Gene, mAPP[A673T], on Amyloid-β Plaque Burden in the 5×FAD Alzheimer Model.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {1},
pages = {48581},
doi = {10.31083/JIN48581},
pmid = {41609044},
issn = {0219-6352},
support = {PAR1577//TauRx Therapeutics Ltd., Singapore/ ; PAR2074//TauRx Therapeutics Ltd., Singapore/ ; },
mesh = {Animals ; *Alzheimer Disease/genetics/pathology/metabolism ; *Amyloid beta-Protein Precursor/genetics/metabolism ; Disease Models, Animal ; *Plaque, Amyloid/pathology/genetics/metabolism ; Mice, Transgenic ; Male ; *Amyloid beta-Peptides/metabolism ; Mice, Inbred C57BL ; Female ; Presenilin-1/genetics ; Mice ; Humans ; Mutation ; *Brain/pathology/metabolism ; Iceland ; },
abstract = {BACKGROUND: The protective Icelandic mutation in the amyloid precursor protein (APP) gene, APP[A673T], identified in Icelandic and other Nordic populations is associated with a significantly lower risk of developing Alzheimer's disease (AD). Conflicting results have been reported for the human APP[A673T] mutation in various knock-in models of AD, but the effect of the mouse APP[A673T] form in 5× familial AD (5×FAD) mice has never been investigated.

METHODS: We crossed C57Bl6/J mice expressing a single point mutation edited into the murine APP gene via Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated (CRISPR-Cas) gene editing, termed mAPP[A673T], with 5×FAD mice that overexpress human APP carrying the Swedish (K670N/M671L), Florida (I716V), and London (V717I) mutations as well as human presenilin-1 (PS1) with two mutations (M146L and L286V); the resulting mice were termed 5×FAD × mAPP[A673T] mice. We investigated amyloid beta-protein (Aβ) pathology in 5×FAD × mAPP[A673T], 5×FAD and their respective controls, mAPP[A673T], and C57Bl6/J wild type mice, at 6-months of age using immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay (ELISA).

RESULTS: We found a moderate yet significant reduction in Aβ plaque size in male 5×FAD × mAPP[A673T] compared with 5×FAD mice. No differences were observed for soluble/insoluble Aβ40 and Aβ42 levels per se, but lower plaque count/area was found in 5×FAD × mAPP[A673T] mice when Aβ42/Aβ40 ratios were low, suggesting a genotype-dependent sensitivity to Aβ aggregation and accumulation.

CONCLUSIONS: The mAPP[A673T] mutation has the potential to modify Aβ pathology in 5×FAD mice at the age of 6 months.},
}

Animals
*Alzheimer Disease/genetics/pathology/metabolism
*Amyloid beta-Protein Precursor/genetics/metabolism
Disease Models, Animal
*Plaque, Amyloid/pathology/genetics/metabolism
Mice, Transgenic
Male
*Amyloid beta-Peptides/metabolism
Mice, Inbred C57BL
Female
Presenilin-1/genetics
Mice
Humans
Mutation
*Brain/pathology/metabolism
Iceland

@article {pmid41609039,
year = {2026},
author = {Luo, Y and Liu, Y and Long, H and Pei, C and Mao, L and Rose, GM and Zhang, H},
title = {Adipose-Derived Stem Cells Transfected to Express Brain-Derived Neurotrophic Factor Reduce Hippocampal Amyloid Plaque Load and Improve Dendritic Morphology in the APP/PS1dE9 Mouse Model of Alzheimer's Disease.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {1},
pages = {46077},
doi = {10.31083/JIN46077},
pmid = {41609039},
issn = {0219-6352},
support = {XSTS2025125//Academic Enhancement Support Program of Hainan Medical University/ ; ZDYF2022SHFZ290//Hainan Province Science and Technology Special Fund of China/ ; },
mesh = {Animals ; *Brain-Derived Neurotrophic Factor/metabolism/genetics ; *Alzheimer Disease/therapy/metabolism/pathology ; Disease Models, Animal ; *Hippocampus/metabolism/pathology ; Mice ; *Plaque, Amyloid/pathology/metabolism/therapy ; *Dendrites/pathology/metabolism ; Mice, Transgenic ; Transfection ; Adipose Tissue/cytology ; *Stem Cell Transplantation/methods ; Male ; Amyloid beta-Protein Precursor/genetics ; },
abstract = {BACKGROUND: Recent studies have indicated that stem cells could provide therapeutic benefits in several neurological conditions, including Alzheimer's disease (AD). Adipose-derived stem cells (ADSCs) offer many advantages in that they are readily available from individual hosts, are robust, and secrete many factors that promote neuronal growth and homeostasis.

METHODS: We transfected ADSCs with a viral construct for brain-derived neurotrophic factor (BDNF) and examined the effects of transplanting these cells into the hippocampus of 7-mo-old APPswe/PS1dE9 mice. After 6 mo, the hippocampus was examined for stem-cell survival, effects on BDNF and neprilysin-2 (NEP-2) levels, dendritic morphology using microtubule associated protein 2 (MAP2) immunohistochemistry, and amyloid plaque load.

RESULTS: We found that transplanted BDNF-ADSCs had survived after 6 mo. BDNF and NEP-2 levels were higher than sham controls, and dendritic architecture was improved. In addition, amyloid plaque numbers were reduced.

CONCLUSIONS: BDNF-ADSCs appear to confer benefits by simultaneously enhancing amyloid clearance and promoting neuronal structural repair. This multifaceted approach highlights the potential of engineering stem cells to target multiple pathophysiological hallmarks of AD, positioning BDNF-ADSCs as a powerful and synergistic cell-gene therapy strategy for this devastating disorder.},
}

Animals
*Brain-Derived Neurotrophic Factor/metabolism/genetics
*Alzheimer Disease/therapy/metabolism/pathology
Disease Models, Animal
*Hippocampus/metabolism/pathology
Mice
*Plaque, Amyloid/pathology/metabolism/therapy
*Dendrites/pathology/metabolism
Mice, Transgenic
Transfection
Adipose Tissue/cytology
*Stem Cell Transplantation/methods
Male
Amyloid beta-Protein Precursor/genetics

@article {pmid41609036,
year = {2026},
author = {Dai, S and Yuan, S and Zhang, X and Zhong, X and Jiang, C},
title = {Effect of Physical Activity on Cognitive Function of Patients With Alzheimer's Disease: A Meta-analysis.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {1},
pages = {42702},
doi = {10.31083/JIN42702},
pmid = {41609036},
issn = {0219-6352},
support = {32371132//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Alzheimer Disease/rehabilitation/therapy ; *Exercise/physiology ; *Exercise Therapy/methods ; *Cognition/physiology ; Randomized Controlled Trials as Topic ; },
abstract = {BACKGROUND: Physical activity (PA) is a widely accepted non-pharmacological therapy for patients with Alzheimer's disease (AD). Existing studies have demonstrated that PA can improve cognitive function in AD patients. However, few of the meta-analyses conducted to date have included participants with a confirmed AD diagnosis that meets standardized diagnostic criteria, nor have they systematically evaluated the interactions between different intervention parameters. The aim of this study was therefore to investigate the effects of PA on cognitive function improvement in AD patients, and how different intervention parameters may influence the effect sizes.

METHODS: Two investigators independently conducted systematic searches in four international databases (PubMed, Web of Science, Embase, and Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure [CNKI] and VIP Database [VIP]) while adhering to PRISMA guidelines. The search was limited to randomized clinical trials (RCTs) and covered each database from its inception to March 31, 2025. The methodological quality of included studies was assessed using criteria from the Cochrane Handbook 5.1.0. All analyses were performed using Stata 15.0.

RESULTS: The meta-analysis included 13 RCTs with a total of 813 AD patients. PA significantly improved Mini-Mental State Examination (MMSE) scores in AD patients (Weighted Mean Difference [WMD] = 1.79, 95% CI: 1.03 to 2.55, p < 0.001). Subgroup analyses showed that interventions with moderate intensity (WMD = 2.12), a single session duration of 30 min (WMD = 2.15), a frequency of >3 times per week (WMD = 3.03), a total weekly intervention time of >120 min (WMD = 2.10), and a total intervention duration of >12 weeks (WMD = 1.95) significantly improved MMSE scores. Meta-regression analysis revealed that intervention frequency (p < 0.001) and total intervention duration (p = 0.002) were significantly correlated with improved cognitive function, while the intervention intensity (p < 0.001) and single session duration (p = 0.002) showed negative correlations.

CONCLUSIONS: Our findings suggest that PA interventions can improve MMSE scores and enhance cognitive function in AD patients. We recommend that PA interventions for AD patients consist of moderate-intensity, a single session duration of 30 min, a frequency of >3 times per week, a total weekly intervention time of >120 min, and a total intervention duration of >12 weeks. The PROSPERO Registration: CRD420250631766. https://www.crd.york.ac.uk/PROSPERO/view/CRD420250631766.},
}

Humans
*Alzheimer Disease/rehabilitation/therapy
*Exercise/physiology
*Exercise Therapy/methods
*Cognition/physiology
Randomized Controlled Trials as Topic

@article {pmid41609034,
year = {2026},
author = {Gashtrodkhani, AA and Shirkouhi, SG and Khatami, SS and Kamari, F and Ghaedi, S and Blaabjerg, M and Andalib, S},
title = {Neuroplasticity and Alzheimer's Disease.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {1},
pages = {48051},
doi = {10.31083/JIN48051},
pmid = {41609034},
issn = {0219-6352},
mesh = {Humans ; *Neuronal Plasticity/physiology ; *Alzheimer Disease/physiopathology/therapy ; Animals ; *Brain/physiopathology ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disease that leads to a decline in cognitive function, including memory. The exact causes of AD are not fully understood, and to date no treatments are available that can stop the progression of this neurocognitive disorder. AD is associated with progressive loss of neurons, synaptic connectivity, and disruption of neuroplasticity in the brain. Neuroplasticity is the nervous system's ability to adapt and recover in response to experiences, injuries, or a pathological change. Synaptic dysfunction and impairment of neuroplasticity are important elements of AD progression and cognitive decline. Studies have demonstrated that enhancement of neuroplasticity effectively improves cognition and memory, preventing the progression of AD. In this narrative review, we discuss the role of various pathophysiological explanations regarding the impairment of neuroplasticity in the pathogenesis of AD. We also highlight neuromodulation approaches, such as exercise, neurotrophic factor mimetics, pharmacological drugs, light therapy, and diet therapy that can promote neuroplasticity and have the potential for use in the prevention and treatment of AD.},
}

Humans
*Neuronal Plasticity/physiology
*Alzheimer Disease/physiopathology/therapy
Animals
*Brain/physiopathology

@article {pmid41608987,
year = {2026},
author = {Tsai, WY and Giesbertz, P and Breimann, S and Lichtenthaler, S and Frishman, D},
title = {Multi-platform integration of brain and CSF proteomes reveals biomarker panels for Alzheimer's disease.},
journal = {Briefings in bioinformatics},
volume = {27},
number = {1},
pages = {},
doi = {10.1093/bib/bbag012},
pmid = {41608987},
issn = {1477-4054},
support = {//Deutsche Forschungsgemeinschaft/ ; EXC 2145 SyNergy-ID 390857198//Munich Cluster for Systems Neurology/ ; FKZ03LW0246//Federal Ministry of Research, Technology, and Space through CLINSPECT-M/ ; ZT-I-PF-5-094//Helmholtz Association Deeproad/ ; },
mesh = {*Alzheimer Disease/metabolism/cerebrospinal fluid/diagnosis ; Humans ; *Biomarkers/cerebrospinal fluid/metabolism ; *Proteome/metabolism ; *Brain/metabolism ; *Proteomics/methods ; Machine Learning ; },
abstract = {Alzheimer's disease (AD) is the leading cause of dementia and represents a progressive, irreversible neurodegenerative disorder. Given the complexity and heterogeneity of AD, which involves numerous interrelated molecular pathways, large-scale proteomics datasets are essential for robust biomarker discovery. Comprehensive proteomic profiling enables the unbiased identification of novel biomarkers across diverse biological processes, thereby increasing the likelihood of finding sensitive and specific candidates for early diagnosis and therapeutic targeting. In this study, we analyzed 28 large-scale proteomics datasets obtained from the AD Knowledge Portal and published studies. The data comprise tandem mass tag, label-free quantification, and proximity extension assay measurements from brain tissue and cerebrospinal fluid. To enhance analytical power, we integrated these proteomic profiles with corresponding clinical information to construct comprehensive feature sets for subsequent machine learning analysis. Using Random Forest and Logistic Regression models, we identified a panel of proteins capable of distinguishing AD patients from healthy controls. Several of these biomarkers have been previously validated in the context of AD, while others represent novel candidates not yet reported as AD-associated. These newly identified biomarkers warrant further experimental validation and hold promise for improving early diagnosis as well as guiding the development of targeted therapies for AD.},
}

*Alzheimer Disease/metabolism/cerebrospinal fluid/diagnosis
Humans
*Biomarkers/cerebrospinal fluid/metabolism
*Proteome/metabolism
*Brain/metabolism
*Proteomics/methods
Machine Learning

@article {pmid41608866,
year = {2026},
author = {Haque, MA and Hossain, MS and Ramasamy, VS and Park, IS},
title = {Biflavonoids can Potentially Inhibit Amyloid Beta Internalization to Mitigate Its Cytotoxic Events.},
journal = {Molecular nutrition & food research},
volume = {70},
number = {2},
pages = {e70406},
doi = {10.1002/mnfr.70406},
pmid = {41608866},
issn = {1613-4133},
mesh = {*Amyloid beta-Peptides/metabolism/antagonists & inhibitors/chemistry/toxicity ; *Biflavonoids/pharmacology ; Humans ; *Peptide Fragments/metabolism/antagonists & inhibitors/chemistry/toxicity ; Alzheimer Disease/drug therapy/metabolism ; },
abstract = {Amyloid-β-42 (Aβ42) internalization plays a critical role in Alzheimer's disease (AD) pathology. We investigated whether biflavonoids, natural small molecules, could inhibit Aβ42 uptake and mitigate its cytotoxicity. Biochemical and imaging analyses revealed that biflavonoids dose-dependently blocked Aβ42 internalization, preventing lamin fragmentation and caspase activation which are considered as key steps in Aβ42-induced cell death. Confocal microscopy and Western blotting confirmed reduced Aβ42 entry, while aggregation assays in cell-free conditions demonstrated biflavonoids suppress Aβ42 fibril, oligomer, and β-sheet formation. These findings suggest biflavonoids exert cytoprotective effects by inhibiting both Aβ42 conformational changes and cellular uptake, positioning them as promising anti-amyloidogenic agents for AD therapy.},
}

*Amyloid beta-Peptides/metabolism/antagonists & inhibitors/chemistry/toxicity
*Biflavonoids/pharmacology
Humans
*Peptide Fragments/metabolism/antagonists & inhibitors/chemistry/toxicity
Alzheimer Disease/drug therapy/metabolism