@article {pmid41548010,
year = {2026},
author = {Nagaraj, S and Quintanilla-Sánchez, C and Ando, K and Lopez-Gutierrez, L and Gansemans, Y and Doeraene, E and Kosa, AC and Aydin, E and Van Nieuwerburgh, F and Brion, JP and Leroy, K},
title = {Differentially expressed miRNAs in the temporal cortex of Alzheimer's disease patients and their association to tau pathology.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09530-0},
pmid = {41548010},
issn = {2399-3642},
abstract = {Alzheimer's disease (AD) is a major contributor to dementia in the elderly, characterized by progressive impairments in memory and behaviour. AD is marked by pathological hallmarks: amyloid plaques and neurofibrillary tangles (NFTs). Despite extensive efforts to understand these hallmarks, there is still a lack of efficient therapeutic approaches due to limited knowledge of the fundamental cellular mechanisms underlying the disease. One potential avenue of research involves the investigation of the roles of non-coding RNAs, particularly microRNAs (miRNAs), which bind to the 3' UTRs of target mRNAs to suppress expression. In our study, we analyse the temporal superior T1 isocortex of control and AD patients, identifying differentially expressed miRNAs using next-generation sequencing (NGS). To validate these findings, we utilize an additional technique, RT-qPCR. Our study confirms the previous findings on the dysregulation of miR-129-5p, miR-132-3p, and miR-146b-5p, while also provides insights into the dysregulation of miR-151a-5p and miR-1-3p. Importantly, the expression levels of miR-129-5p, miR-146b-5p, miR-132-3p, and miR-151a-5p are significantly correlated with the neuropathological Braak stages and with biochemically quantified tau phosphorylation levels in brain homogenates. Additionally, we find that miR-146b-5p and miR-151a-5p significantly modulate tau seeding in tau biosensor cell model, highlighting their potential roles in tau pathology.},
}

@article {pmid41547856,
year = {2026},
author = {Zhang, X and Yu, Z and Hao, G and Yao, Q and Hu, Y and Wang, F and Chen, X and Liu, L and Wong, KC and Li, X},
title = {Robust characterization and interpretation of rare pathogenic cell populations from spatial omics using GARDEN.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68500-6},
pmid = {41547856},
issn = {2041-1723},
support = {62472195//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Spatial omics links molecular measurements to their positions in tissue, revealing cellular organization and interactions. Yet most computational tools highlight common cell types and overlook rare populations that can drive disease. Here we show GARDEN, a computational framework that identifies and characterizes these pathogenic cells or regions in spatial omics by embedding graph-based dynamic attention into a spatially-aware graph fusion contrastive model. GARDEN works consistently across tissues, species and resolution scales, and aligns consecutive sections to reconstruct 3D anatomy. In an Alzheimer's disease model, GARDEN localizes C1qa/C1qb-marked microglia in amyloid-β regions and reveals key immune pathways. In nasopharyngeal carcinoma it identifies tiny tertiary lymphoid structures, and in breast cancer it uncovers inflammatory M1-like macrophages near ductal carcinoma in situ and links them to pro-metastatic signaling. An interpretation module pinpoints key immune signatures, and GARDEN extends to spatial chromatin accessibility, providing insight into epigenetic regulation and informing diagnostics and therapeutic targeting.},
}

@article {pmid41547853,
year = {2026},
author = {Yanes, KJO and Bui, CT and Tomasello, J and Morsy, H and Kim, E and Lam, T and Tsourmas, K and Ayala, LA and Green, KN and Inlay, MA and Lodoen, MB},
title = {Toxoplasma gondii drives myeloid immune cell recruitment to amyloid plaques in Alzheimer's model mice.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03666-2},
pmid = {41547853},
issn = {1742-2094},
abstract = {Infections in the central nervous system result in immune cell trafficking into the brain and microglial activation, which may influence Alzheimer's Disease neuropathology. Toxoplasma gondii infection induces a robust neuroimmune response and a reduction in amyloid plaques in the brains of Alzheimer's model mice. We investigated the myeloid cell response in the immediate vicinity of amyloid plaques in the brain by injecting 3-month-old 5xFAD mice with T. gondii or PBS as a control. T. gondii chronic infection (6 weeks) resulted in reduced amyloid plaque area, volume, and intensity in the cortex, and plaques with decreased circularity based on 6E10 and Thio-S staining. The brains of T. gondii-infected mice also had increased AIF1, AXL, and CLEC7A transcripts for disease-associated microglia (DAM), and elevated IBA1, MAC2, and CD68 phagolysosomal colocalization with amyloid, indicating myeloid cell activation around plaques. CD4 and CD8 T cells were also increased near amyloid and IBA1[+] cells in T. gondii-infected mice. To determine the extent of peripheral myeloid cell recruitment to amyloid, bone marrow from CAG-CFP mice was transplanted into irradiated, head-shielded 5xFAD mice prior to infection. Cyan[+] cells were found surrounding plaques in the brains of T. gondii-infected mice and were comprised predominantly of Ly6C[lo] patrolling monocytes, followed by Ly6C[hi] inflammatory monocytes and T cells. In addition, the majority of myeloid cells and T cells recruited to the brain were derived from skull bone marrow. These data demonstrate that T. gondii infection increases the infiltration of monocytes and T cells from the skull bone marrow niche and the recruitment of highly activated myeloid cells surrounding amyloid plaques in the brains of 5xFAD mice.},
}

@article {pmid41547736,
year = {2026},
author = {Lobo, JD and Serrano, VB and Campbell, LM and Bell, T and Gouaux, B and Galasko, D and Letendre, S and Bondi, MW and Moore, DJ and Sundermann, EE},
title = {Cerebrospinal fluid markers of alzheimer's pathology relate to aMCI among people with HIV.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-025-04585-8},
pmid = {41547736},
issn = {1471-2377},
support = {K01DA060092/DA/NIDA NIH HHS/United States ; R01MH125720/MH/NIMH NIH HHS/United States ; H22D4432//California HIV/AIDs Research Program/ ; RF1[AG061070]//NIH NNTC/ ; RF1[AG061070]//NIH NNTC/ ; },
}

@article {pmid41547581,
year = {2026},
author = {Fan, SP and Liu, PC and Wang, JZ and Lin, CH and Lin, HH},
title = {Disease burden of neurodegenerative disorders in Taiwan.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.01.020},
pmid = {41547581},
issn = {0929-6646},
abstract = {BACKGROUND: With global aging, neurodegenerative disorders, particularly Alzheimer's disease (AD) and Parkinson's disease (PD), have become major public health concerns. However, the evaluation of their burden trends in Taiwan is lacking. We assessed temporal and geographic trends in the burden of AD with other dementias and PD in Taiwan from 2000 to 2021, stratified by age, sex, and region.

METHODS: Data from Taiwan's National Health Insurance (NHI) and National Death Registry were analyzed for 2000-2021. Case definitions for Alzheimer's disease with other dementias (ADODs) and Parkinson's disease (PD) followed Global Burden of Disease 2021 criteria and were identified using ICD codes. Fatal burden was assessed using the National Death Registry. Disease burden was quantified by years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs), with additional geographic mapping to visualize regional variations.

RESULTS: Between 2000 and 2021, age-standardized prevalence rose sharply for ADODs (+885 %) and PD (+394 %), while mortality increased by 116 % and 31 %, respectively; incidence remained stable. DALY rates grew by 258 % for ADODs and 86 % for PD, mainly driven by rising YLDs. The greatest burden was among those aged ≥80 years, with ADODs and PD DALYs increasing by 357 % and 147 %, respectively. Geographically, the highest age-standardized DALYs for ADODs and PD were found in the Southern Taiwan.

CONCLUSION: The prevalence and health burden of ADODs and PD have increased substantially in Taiwan despite declining incidence, posing growing challenges to the aging population.},
}

@article {pmid41547342,
year = {2026},
author = {Huo, M and Kim, K and Brown, CK and Gilligan, M and Wang, W},
title = {Receiving caregiver support and its association with hair hormones in people living with Alzheimer's disease: The role of caregivers' perspective taking.},
journal = {Psychoneuroendocrinology},
volume = {186},
number = {},
pages = {107746},
doi = {10.1016/j.psyneuen.2026.107746},
pmid = {41547342},
issn = {1873-3360},
abstract = {Receiving support in later life is often experienced as stressful, but for people living with dementia (PLWD) support is an unavoidable necessity for daily functioning. The current study examined the association between receiving support in this unique context and PLWD's hair cortisol, dehydroepiandrosterone (DHEA), and DHEA-to-cortisol ratio, which serve as non-invasive, objective physiological measures that may reflect longer-term HPA-axis activity related to stress. Further, we explored whether caregivers' perspective taking-their ability to understand PLWD's thoughts and feelings-moderated associations between support receipt and hair hormones. Participants included 58 couples managing mild-to-moderate Alzheimer's disease (Mage = 77.60 for PLWD; Mage = 75.48 for caregivers). PLWD self-reported the frequency of emotional and practical support received from their spousal caregivers. Hair samples were collected from the posterior vertex to assess cortisol and DHEA concentrations and were assayed using enzyme immunoassay (EIA) method. Caregivers reported their own perspective taking and both spouses' demographic characteristics. Multiple regressions showed that receiving more frequent emotional support and less frequent practical support from spousal caregivers were associated with higher hair cortisol concentrations in PLWD. Yet, these associations were only evident if caregivers had greater perspective taking. In addition, caregiver perspective taking exacerbated the negative association between receiving emotional support and the DHEA-to-cortisol ratio. By using hair hormones, this study offers preliminary insights into PLWD's stress-related physiological processes in the context of intensive caregiving. Findings refine our understanding of the benefits and costs of caregivers' perspective taking and inform caregiver interventions.},
}

@article {pmid41547327,
year = {2026},
author = {Zothantluanga, JH and Chagaleti, BK and Roy, D and Abdalla, M and El-Arabey, AA and Alahmady, NF and Jha, NK},
title = {Dual inhibition of AChE and GSK-3β by flavonoids of Bergenia ciliata: Molecular dynamics insights into anti-Alzheimer's activity.},
journal = {Computational biology and chemistry},
volume = {122},
number = {},
pages = {108908},
doi = {10.1016/j.compbiolchem.2026.108908},
pmid = {41547327},
issn = {1476-928X},
abstract = {Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and is also responsible for more than half of all dementia cases. In our ongoing efforts to identify promising phytocompounds as potential modulators of AD-related molecular targets, we studied 53 phytocompounds from Bergenia ciliata, a medicinal plant known for its in vivo anti-Alzheimer activity. Acetylcholinesterase (AChE), GSK-3β, and β-site amyloid precursor protein cleaving enzyme (BACE1) were the target proteins. Molecular docking and 100 ns molecular dynamics (MD) simulations revealed that 3-O-galloylcatechin and 3-O-galloylepicatechin showed favorable interactions with AChE and GSK-3β, as they were able to outperform the positive controls in all of the studied parameters. However, the MM-GBSA binding free energy calculations revealed that only 3-O-galloylepicatechin, but not 3-O-galloylcatechin, outperformed the positive control of GSK-3β. Density functional theory (DFT) studies revealed that 3-O-galloylcatechin and 3-O-galloylepicatechin were stable and chemically reactive at the active sites of AChE and GSK-3β. The in-silico findings suggest that the observed in-vivo anti-Alzheimer activity of B. ciliata may be partly associated with the favorable molecular interactions of 3-O-galloylcatechin and 3-O-galloylepicatechin with AChE and GSK-3β. The current findings highlight the structural and mechanistic relevance of B. ciliata phytocompounds in modulating AD-associated targets. Based on the current findings, medicinal plants that contain 3-O-galloylcatechin and 3-O-galloylepicatechin may also be screened for their interactions with AD-related molecular targets.},
}

@article {pmid41547315,
year = {2026},
author = {Wang, J and Zhang, N and Tu, Z and Wu, Z and Yang, J and Chen, X and Lu, Y and Le, W and Luo, R},
title = {Chlorpyrifos induced dysregulation of arginine biosynthesis pathway aggravates Alzheimer's disease progression in 5XFAD mice via microbiota-gut-brain axis crosstalk.},
journal = {Environment international},
volume = {208},
number = {},
pages = {110064},
doi = {10.1016/j.envint.2026.110064},
pmid = {41547315},
issn = {1873-6750},
abstract = {Epidemiological evidence suggests that occupational or environmental exposure to Chlorpyrifos (CPF) is associated with Alzheimer's disease (AD)-like behaviors. However, the exact mechanisms remain elucidate. This study investigates the impact of environmentally relevant concentrations of CPF on AD progression in 5XFAD mice and explores potential intervention strategies. Our results demonstrate that CPF exposure exacerbates AD symptoms in 5XFAD mice, characterized by cognitive deficits, increased amyloid-β accumulation, neuroinflammation, and neuron loss. Mechanistically, CPF induces gut microbiota dysbiosis in 5XFAD mice, with significant decreases in beneficial taxa such as Muribaculaceae and Faecalibaculum, and a marked increase in pathogenic genus Tyzzerella. This dysbiosis leads to intestinal structural damage, compromised barrier function, and disruption of arginine biosynthesis pathway. Therefore, disruption of this pathway in gut microbiota metabolites results in a significant decrease in L-Citrulline (L-Cit) concentration, thereby causing a marked reduction in serum L-Arginine (L-Arg) levels. Importantly, these altered metabolites upregulate the transcription of hippocampal neuroinflammation-related pathway spectrum, particularly through significant upregulation of Casp1 and Ccl3, indicating the occurrence of neuroinflammation. L-Cit supplementation significantly increase serum L-Arg levels in CPF-exposed 5XFAD mice, thereby alleviating AD pathology and improving cognitive function. Collectively, these findings reveal a novel arginine metabolism-mediated mechanism along the microbiota-gut-brain axis in CPF-mediated AD pathogenesis and underscore the therapeutic potential of L-Cit for CPF-related neurodegenerative disorders.},
}

@article {pmid41547241,
year = {2025},
author = {Reichau, K and Crouzier, L and Gehrig, T and Flake, A and Schaller, E and Meunier, J and Bertrand-Gaday, C and Chatonnet, A and Zvejniece, L and Sotriffer, C and Maurice, T and Decker, M},
title = {Targeting neuroinflammation by activation of the sigma-1 receptor (S1R) and inhibition of butyrylcholinesterase (hBChE) leads to highly potent anti-amnesic compounds in an Alzheimer's disease mouse model.},
journal = {European journal of medicinal chemistry},
volume = {305},
number = {},
pages = {118486},
doi = {10.1016/j.ejmech.2025.118486},
pmid = {41547241},
issn = {1768-3254},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder for which no effective preventative or curative treatment has yet been identified. Due to the multifactorial nature and complex pathophysiology of the disease, we developed a multi-target ligand that both inhibits human butyrylcholinesterase (hBChE), a key enzyme linked to β-amyloid plaque formation, and activates the sigma-1 receptor (S1R), which modulates neuroinflammatory and protective pathways. To this end, a series of isoindolines were designed and synthesized, and their biological activities were evaluated. The most promising compound, 7c, exhibited significant dual activity, achieving nanomolar IC50 values against hBChE and potent S1R activation. Subsequent in vivo studies in an Aβ25-35 mouse model revealed a remarkable improvement in cognitive deficits in both short- and long-term memory at an effective dose of 0.01 mg/kg in WT Swiss-OF1 mice. This dose is 10-fold lower compared to single-target compounds 7a and 7b of this isoindoline series. The lack of neuroprotective effects in BChE knock-out (KO) mice confirmed the involvement of BChE inhibition in the pharmacological effects of compound 7c in WT mice. Further combinatorial studies employing a two-drug combination demonstrated synergy in the neuroprotective effect of addressing the two targets.},
}

@article {pmid41547191,
year = {2026},
author = {Ji, Q and Liu, Q and Xu, Y and Xu, M and Zhan, Y},
title = {Long-term exposure to residential greenspace, bluespace, traffic, and air pollutants with dementia: A prospective cohort study with exploratory mediation by plasma metabolites and telomere length.},
journal = {Ecotoxicology and environmental safety},
volume = {310},
number = {},
pages = {119750},
doi = {10.1016/j.ecoenv.2026.119750},
pmid = {41547191},
issn = {1090-2414},
abstract = {BACKGROUND: Residential environmental factors-including air pollution, traffic, greenspace, and bluespace-have been increasingly linked to dementia risk, yet the joint impacts and biological pathways remain underexplored. This study aimed to examine the associations between these diverse residential exposures and all-cause and cause-specific dementia, while exploring the mediating roles of plasma metabolites and telomere length.

METHODS: Using the UK Biobank (UKB) cohort, we analyzed 317,498 participants free of dementia at baseline. Exposures were assessed via geographic and model-based data, and outcomes included all-cause dementia (ACD), Alzheimer's disease (AD), vascular dementia (VaD), and other dementia subtypes (O). Cox proportional hazards models were applied to estimate the associations between exposures and dementia outcomes. Separate mediation analyses were conducted to examine the potential mediating roles of plasma metabolites and telomere length.

RESULTS: Pollutant exposures, especially NO₂ and PM10, were consistently associated with higher dementia risk, with age-specific patterns. Greenspace showed inverse associations, notably for ACD and VaD, while traffic proximity elevated VaD risk. Exploratory mediation suggested 49 metabolites for the PM2.5-10-ACD association in participants under 65, with the largest proportions for Omega-3 % (33.29 %) and S-VLDL-TG% (32.99 %).

CONCLUSION: Air pollution, especially particulate matter, was significantly associated with dementia risk, partially mediated by metabolic pathways. These findings underscore the importance of environmental interventions in dementia prevention.},
}

@article {pmid41547121,
year = {2026},
author = {Liu, H and Gui, Y and Zhao, B and Lu, H and Liu, M},
title = {A causal bidirectional selective state space model for imaging genetics in neurodegenerative diseases.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {198},
number = {},
pages = {108587},
doi = {10.1016/j.neunet.2026.108587},
pmid = {41547121},
issn = {1879-2782},
abstract = {Brain imaging genetics aims to uncover the pathological mechanisms and improve the diagnosis of brain diseases, particularly neurodegenerative disorders. While deep learning has advanced feature extraction and association modeling in this field, there are still two major challenges: extracting meaningful information from long genetic sequences and establishing causal relationships among genetics, imaging, and disease. To address these challenges, this paper proposes a deep causal bidirectional selective state space model (CausalMamba) that integrates multi-level feature extraction and causal inference into a unified representation learning framework. First, the long-sequence genetic data and whole-brain imaging data are divided into localized parts, extracting the fine-grained features. Then, a causal inference strategy based on counterfactual reasoning and contrastive learning is proposed to identify the most relevant genetic and imaging features and to construct a causal chain from genetics to disease via imaging. Finally, a bidirectional selective state space model (BiMamba) efficiently integrates the selected features into modality-specific global features, enabling accurate disease diagnosis. Our model is trained jointly on genetic and imaging data, but requires only genetic data at test time. We validate the proposed method on the simulated dataset, Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and Parkinson's Progression Markers Initiative (PPMI) dataset. Experimental results show that our method achieves accuracies of 80.5% and 77.3% using only genetic data in classifying Alzheimer's and Parkinson's diseases from normal controls, respectively, with the relative improvements of 4.2% and 2.7% over the state-of-the-art methods while also being more computationally efficient. The results demonstrate that CausalMamba can effectively identify causally relevant biomarkers across the entire genome and brain.},
}

@article {pmid41547056,
year = {2026},
author = {Finlay, J and Savard, G and Alvarez-McNelis, D and Sagehorn, M and Bowman, G and Sun, Y and Esposito, M},
title = {Cognability across adulthood: A qualitative investigation of neighborhoods and cognitive health behaviors.},
journal = {Social science & medicine (1982)},
volume = {392},
number = {},
pages = {118971},
doi = {10.1016/j.socscimed.2026.118971},
pmid = {41547056},
issn = {1873-5347},
abstract = {While geographic variation in Alzheimer's Disease and Related Dementias (ADRD) rates suggests that environmental factors are important in the development of dementia, understanding of specific neighborhood sites that impact dementia risk is limited, especially in early and mid adulthood. This paper extends Cognability to a life course perspective to conceptualize how neighborhoods may support cognitive health behaviors including physical activity, diet, cognitive stimulation, and socialization across adulthood. The Neighborhoods and Health at All Ages Study employed stationary and mobile interviews (August 2023-March 2024) across the Minneapolis-St. Paul (MN) metropolitan area. Participants were on average 42 years old (range: 23-75). About half (53 %) identified as female, 40 % male, and 7 % nonbinary. Participants reflected diverse racial and ethnic backgrounds, including Asian (22 %), Hispanic (22 %), non-Hispanic White (18 %), Multiracial (17 %), Black/African American (15 %), American Indian/Alaska Native (3 %), and Other/Missing (3 %). Reflexive thematic analysis identified ten neighborhood services and amenities that support cognitive health behaviors: parks and paths, recreation centers, eateries, grocers and food markets, retail stores, civic and social organizations, religious organizations, arts and cultural sites, libraries, and educational sites. The study captured nuanced, intersectional perspectives from adults with varied socioeconomic, racial/ethnic, and gender identities to illuminate how use and salience of neighborhood services and amenities vary across adulthood. As the global dementia burden grows and disparities widen, our results help inform upstream community-level interventions to create more equitable neighborhoods that reduce ADRD risk and support lifelong cognitive health and wellbeing.},
}

@article {pmid41546974,
year = {2026},
author = {Zhang, Y and Zhao, L and Yu, X and Liu, H and Zhao, M},
title = {Single-vesicle profiling of multiple biomarkers on serum EVs via EV-CATCH and nano-flow cytometry for clinical stratification of Alzheimer's disease.},
journal = {Biosensors & bioelectronics},
volume = {298},
number = {},
pages = {118399},
doi = {10.1016/j.bios.2026.118399},
pmid = {41546974},
issn = {1873-4235},
abstract = {Alzheimer's disease (AD) is a kind of progressive neurodegenerative disorder caused by neuron damage, which imposed significant economic and social burdens. Early and precise AD diagnosis remains an obstacle in the clinic, primarily attributable to the absence of simple, noninvasive, and reliable detection methods. Extracellular vesicles (EVs) carry molecular cargos reflecting cellular origin and can cross the blood-brain barrier, serving as promising biomarkers for neurological diseases. Herein, we propose a novel EV-CATCH-based nano-flow cytometry strategy for rapid, noninvasive, and single-vesicle profiling of multiple AD-related protein biomarkers on EVs. The EV-CATCH enables controlled capture and on-demand release of serum EVs, ensuring high specificity and structural integrity of the isolated vesicles. Four core AD biomarkers on serum EVs were profiled at the individual vesicle level for stratification, and their clinical utility was assessed in two cohorts. The first cohort included 29 Aβ-PET-negative and 42 Aβ-PET-positive participants. In this group, the biomarker panel demonstrated an AUC of 0.873 in differentiating Aβ-PET status, further supporting its value in reflecting cerebral amyloid pathology. The second cohort consisted of 110 serum samples, comprising those from healthy controls as well as from subjects with mild cognitive impairment (MCI) and AD. Combined analysis of the four EV-associated biomarkers yielded high diagnostic accuracy, with areas under the receiver operating characteristic curves (AUCs) of 0.932 for MCI and 0.923 for AD. This clinically accessible single-vesicle method enables multiplexed and sensitive EV profiling for early AD diagnosis, accurate disease stratification and longitudinal monitoring, facilitating timely intervention thus promoting better patient prognosis.},
}

@article {pmid41546910,
year = {2026},
author = {Elyasi, L and Wężyk, M},
title = {Exosome-derived microRNAs from stem cells from human exfoliated deciduous teeth (SHED): Emerging therapeutics for neurodegenerative disorders.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {195},
number = {},
pages = {119001},
doi = {10.1016/j.biopha.2026.119001},
pmid = {41546910},
issn = {1950-6007},
abstract = {Neurodegenerative diseases (NDDs) cause progressive damage of brain structures, resulting in a loss of function and, eventually, the patient's death. Current therapeutic strategies are limited to late stages of the disease, culminating in palliative care, while tackling the underlying causes of neurodegeneration could halt or at least slow down the disease at an early stage. In this vein, stem cell transplantation therapies are emerging as a promising alternative, as such as cells can penetrate the central nervous system, engraft, differentiate, and secrete neurotrophic, neuro-regenerative, and neuroprotective factors. Stem cells derived from human exfoliated deciduous teeth (SHED) have demonstrated significant regenerative potential in various biological systems and pathological conditions, showing high proliferative capacity and multipotency to differentiate into neuronal cells both in vivo and in vitro, apparently functioning through exosome-derived microRNAs (exos-miRs). Here, we summarize recent reports on specific miRs from SHED's exosomes, which exert diverse regulatory functions counteracting oxidative stress, and provide immunomodulatory and neurotrophic benefits contributing to the treatment of neurodegeneration in NDDs. We discuss clinical and preclinical evidence supporting the potential of SHED cells in the treatment of NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury, focal cerebral ischemia, and peripheral nerve damage. We also highlight that the use of SHED in NDDs treatment remains largely underexplored, opening a wide field for further research. We suggest deeper studies on the role of SHED-exos-miRs in NDDs, including their proneurotrophic activity, reduction of genotoxic neuronal stress, and disruption of proinflammatory signaling pathways.},
}

@article {pmid41546373,
year = {2026},
author = {Massoumzadeh, P and Tiemann-Powles, S and Naghashzadeh, M and Rizzo, J and Hu, J and Yaeger, LH and Alkelani, H and Wang, Q and Chen, G and Dolatshahi, M and Joseph-Mathurin, N and Benzinger, TLS},
title = {Sex Differences in Alzheimer's Disease: A Systematic Review of Two Decades of Neuroimaging Research.},
journal = {The British journal of radiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/bjr/tqag011},
pmid = {41546373},
issn = {1748-880X},
abstract = {OBJECTIVES: Given the heterogeneous nature of Alzheimer's Disease (AD) and its higher prevalence in females, it is crucial to understand sex-related differences in AD presentation and changes in the brain.

METHODS: : This systematic review investigates sex differences in AD and summarizes key findings from neuroimaging studies over the past two decades to examine how genetics, hormones, and lifestyle factors influence neuroimaging biomarkers and their correlation with cognitive decline and AD progression. A comprehensive literature search was conducted across several databases for human studies from 2004 to 2024 related to AD, biological sex differences, and neuroimaging.

RESULTS: : After a three-step review process, the final extraction included 120 peer-reviewed studies using various neuroimaging modalities, such as Magnetic Resonance Imaging (MRI), amyloid-beta Positron Emission Tomography (PET), tau-PET, and Fluorodeoxyglucose (FDG) PET, to investigate sex as a biological predictor variable in adults with or at risk for AD. Over 90% of the reviewed studies identified clear sex-specific patterns of imaging biomarkers related to cognitive reserve, hormonal changes, APOE-ɛ4 genotype, inflammation, vascular health, and lifestyle factors. Machine learning studies increasingly incorporate sex as a key variable, revealing sex-specific biomarkers and improving model performance in predicting disease status and progression.

CONCLUSIONS: Considering biological sex in AD research is essential for improving diagnostic accuracy, tailoring interventions, and health outcomes.

ADVANCES IN KNOWLEDGE: This systematic review identifies sex-specific patterns in neuroimaging biomarkers of Alzheimer's Disease, influenced by cognitive reserve, hormones, APOE-ɛ4 genotype, inflammation, vascular health, and lifestyle. Recognizing these differences is crucial for understanding, diagnosis, and treatment efficacy.},
}

@article {pmid41546055,
year = {2026},
author = {Ramezani, N and Granberg, S and Kihlgren, A and Baudin, K and Lindner, H},
title = {The use of care home environments to meet culture-specific needs of culturally and linguistically diverse residents with dementia: an integrative review using the ICF framework.},
journal = {International journal for equity in health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12939-025-02748-0},
pmid = {41546055},
issn = {1475-9276},
abstract = {BACKGROUND: Increasing global migration creates new challenges for multicultural societies in providing equitable care. Culturally and linguistically diverse (CALD) people who move into care homes find themselves in an environment where health professionals do not speak their language and the access to cultural activities is limited. This may increase loneliness and social isolation. When designing care home environments for CALD residents with dementia, culture is a key consideration. The aim of this integrative review is to highlight what elements of the care home environment are reported to meet culture-specific needs of CALD residents with dementia, and how.

METHODS: A search strategy which included terms for care homes, forms of dementia and CALD people was developed, and a systematic search was carried out in six databases. Eligible articles were original peer-reviewed studies published between 2013 and 2024 and contained examples of how care home environments have been used to meet culture-specific needs of CALD residents. All screenings and extractions were carried out by two independent researchers.

RESULTS: The search resulted in 4311 records. After the screening process, 27 articles met the eligibility criteria. The review findings are categorized according to components of the WHO's International classification of functioning, disability and health (ICF). Results linked to the ICF component Activities and participation stress the importance of communication in the resident's preferred language, social and supportive relationships and culturally relevant activities, while the component Environmental factors highlights the significance of ethnic food and support from culturally competent care professionals and family members.

CONCLUSIONS: This integrative review underlines the complexity of using environments to meet culture-specific needs of CALD residents with dementia. The findings highlight the importance of bilingual staff, culturally relevant activities and inclusive environments in enhancing communication, building interpersonal relationships and reducing frustration among CALD residents. Collaborations between culturally competent staff, family members and members of cultural communities also facilitate meeting social and cultural needs of these residents. This review offers suggestions on how environments in care homes can be adapted for CALD residents and encourages further research to find practical solutions for equitable care.

REGISTRATION: A study protocol is registered on Prospero (CRD42023492906).},
}

@article {pmid41545942,
year = {2026},
author = {Sun, W and Luan, H and Li, S and Wang, P and Gong, J and Xu, C and Han, X and Wen, B and Lv, S and Wei, C},
title = {Circulating adipokines level and the risk of neurodegenerative diseases: a two‑sample mendelian randomization study and proteomic analysis.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04636-8},
pmid = {41545942},
issn = {1471-2377},
support = {2017YFC1310103//the National Key Research and Development Program of China/ ; 2021ZD0201802//the STI2030-Major Projects/ ; },
}

@article {pmid41545891,
year = {2026},
author = {Singh, SK and Antoine, C and Tse, C and Ji, L and Reed, M and Carter, WG and Trezza, V and Bid, HK},
title = {Therapeutic potential of acidic cannabinoids: an update.},
journal = {Journal of cannabis research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s42238-026-00387-y},
pmid = {41545891},
issn = {2522-5782},
support = {U54CA118638/CA/NCI NIH HHS/United States ; DICRIDG-21-072-01-DICRIDG//American Cancer Society/ ; },
abstract = {Cannabis sativa yields a wide range of bioactive compounds, including terpenes, flavonoids, and cannabinoids. Tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and cannabichromenic acid (CBCA) are the acidic biosynthetic precursors of the neutral cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been the subject of much research. This review examines the biosynthesis, decarboxylation, molecular pharmacology, and therapeutic significance of acidic cannabinoids, intending to address a significant knowledge gap. Peer-reviewed literature from major scientific databases was used in a systematic narrative review with an emphasis on investigations of acidic cannabinoid chemistry, pharmacology, pharmacokinetics, and disease-specific applications. According to the reviewed data, acidic cannabinoids exhibit unique biological activities that distinguish them from their neutral counterparts. These include neuroprotective, anti-inflammatory, anticonvulsant, and anti-proliferative actions, which are mediated by molecular targets such as serotonin 5-HT1A receptors, cyclooxygenase-2 (COX-2), transient receptor potential (TRP) channels, and peroxisome proliferator-activated receptor-γ (PPARγ). Acidic cannabinoids are more appealing for therapeutic usage in children and the elderly, considering that they are not intoxicating like THC; however, this distinction applies primarily to non‑heated consumption. Chemical instability, low bioavailability, and a dearth of controlled human trials impede clinical translation despite their potential. According to the findings, acidic cannabinoids are an underutilized yet potentially valuable class of precision medicines. In this study, we outline existing understanding on acidic cannabinoids, discuss their production and transformation, and identify research needs that could influence cannabis science research.},
}

@article {pmid41545748,
year = {2026},
author = {Wang, L and Liu, Y and Li, F and Li, X and Li, L and Zhang, J and Xu, Y},
title = {CX3CL1 in Early Detection of Alzheimer's Disease: Plasma Dynamics Across Age and Disease Stages.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70320},
pmid = {41545748},
issn = {2328-9503},
support = {CSTB2024NSCQ-MSX0945 to YX//the Natural Science Foundation of Chongqing/ ; },
abstract = {BACKGROUNDS: Alzheimer's disease (AD) is characterized by amyloid-beta plaques, tau tangles, and neuroinflammation. C-X3-C motif chemokine ligand 1 (CX3CL1, also known as fractalkine), a neuroimmune chemokine implicated in AD pathogenesis, shows inconsistent alterations in plasma/serum across studies. Specifically examining age-dependency and diagnostic utility, we investigated plasma CX3CL1 levels across the cognitive continuum (cognitively normal [CN], amnestic mild cognitive impairment [aMCI], AD) in a Chinese cohort.

METHODS: A total of 443 participants, including 130 patients with AD, 72 patients with aMCI, and 99 age-and sex-matched CN controls, as well as a cohort of 142 CN subjects of different ages, were enrolled from Chongqing General Hospital. Plasma CX3CL1 levels were determined using Enzyme-Linked Immunosorbent Assay (ELISA). Apolipoprotein E genotypes (APOE) were performed. The correlations between Plasma CX3CL1 levels and cognition test scores or age were analyzed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis.

RESULTS: Plasma CX3CL1 levels significantly increased with age in CN individuals. No significant sex difference was found. Plasma CX3CL1 levels did not differ significantly between APOE ε4 carriers and non-carriers. Stepwise elevation across continuum: CX3CL1 levels showed a significant stepwise increase: CN controls (1.73 ± 0.51 ng/mL) < aMCI (2.40 ± 1.06 ng/mL) < AD (4.15 ± 1.24 ng/mL) (p < 0.001 between all groups). This pattern persisted in both male and female subgroups, between the AD group and the aMCI group, between the AD group and the CN control group (p < 0.001), between the aMCI group and the CN control group, and between the male and female subgroups (p < 0.05). CX3CL1 levels negatively correlated with Mini-Mental State Examination (MMSE) scores and positively correlated with age.

CONCLUSIONS: Plasma CX3CL1 levels exhibit a significant age-dependent increase in cognitively normal individuals, peak in midlife (40-49 years), and demonstrate a stepwise elevation across the AD continuum (CN → aMCI → AD). Strong inverse correlations with cognitive scores in disease groups and high diagnostic accuracy for AD, particularly against CN, support its role as a biomarker reflecting both physiological aging and AD-related pathological decline. Its regulation appears independent of APOE ε4 status. The midlife peak suggests potential relevance for preclinical processes, warranting further investigation of CX3CL1 as a biomarker and therapeutic target.},
}

@article {pmid41545552,
year = {2026},
author = {Shivahare, BD and Rajadurai, H and K, D and Kansal, S and Mathivanan, SK and S K B, S},
title = {An attention-augmented multimodal classification of alzheimer's disease and parkinson's disease vs healthy controls using MRI, EEG, and SNP data.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-32274-6},
pmid = {41545552},
issn = {2045-2322},
abstract = {Due to the late manifestation of structural symptoms and symptomatic overlap, neurodegenerative diseases such as Parkinson's Disease (PD) and Alzheimer's Disease (AD) remain difficult to diagnose accurately. In order to categorize AD and PD in comparison to Healthy Controls (HC), this study suggests a multimodal classification framework that combines genetic Single Nucleotide Polymorphism (SNP) data, structural Magnetic Resonance Imaging (MRI), and functional Electroencephalography (EEG). To improve the model's accuracy and interpretability, the method makes use of an uncertainty estimate module and a novel cross-modality attention mechanism. The framework strives for diagnosis, concentrating on detecting Parkinson's disease (PD) and Alzheimer's disease (AD) in individuals exhibiting modest motor symptoms or early cognitive impairments, which are indicative of the prodromal stage of both conditions. A dataset of 2,500 MRI images, 1,500 EEG recordings, and SNP data for 1,000 subjects drawn from OpenNeuro, PPMI, and the UK Biobank was utilized in extensive analyses. The developed model was contrasted with recent unimodal and multimodal techniques. Our findings exhibit statistically significant increases of 6-12% compared to similar methods, with 95.6% average classification accuracy on AD and 94.8% on PD. The importance of the attention mechanism and both modalities to overall performance is quantified using ablation studies. Quantification of uncertainty also improves interpretability for possible clinical use. These results demonstrate the proper neurodegenerative disease diagnosis when explainable AI elements are paired with stable multimodal fusion.},
}

@article {pmid41545521,
year = {2026},
author = {},
title = {GLP-1s surprise failure in Alzheimer's.},
journal = {Nature biotechnology},
volume = {44},
number = {1},
pages = {7},
doi = {10.1038/s41587-025-02985-2},
pmid = {41545521},
issn = {1546-1696},
}

@article {pmid41545124,
year = {2026},
author = {Cucinotta, L and Pavarino, M and Cannizzaro, F and Sgorbini, B and Rubiolo, P and Sciarrone, D and Mondello, L},
title = {A novel "cut and sew" procedure for the natural reconstitution of essential oils prior to biological assays.},
journal = {Analytica chimica acta},
volume = {1386},
number = {},
pages = {345045},
doi = {10.1016/j.aca.2025.345045},
pmid = {41545124},
issn = {1873-4324},
mesh = {*Oils, Volatile/chemistry/isolation & purification/pharmacology ; Chromatography, Gas/methods ; Butyrylcholinesterase/metabolism ; Biological Assay ; *Cholinesterase Inhibitors/chemistry/pharmacology/isolation & purification ; Mentha piperita/chemistry ; },
abstract = {BACKGROUND: Given the increasing interest in natural compounds for therapeutic applications, understanding the contribution of individual components within complex essential oils (EOs) is crucial. The isolation is often achieved through bio-guided fractionation, typically using flash chromatography to target chemical classes. To refine this, some methods rely on customized reconstitution using reference standards, which is challenging due to issues with preserving natural abundances and enantiomeric ratios.

RESULTS: This study compares conventional flash chromatography with an advanced preparative multidimensional gas chromatography (prep-GC) system, equipped with a novel collection setup. This prep-GC approach enabled the isolation of sub-fractions at the milligram scale for biological assays. Critically, it preserved the natural distribution of chiral components, eliminating the need for standard-based reconstitution and its associated challenges. Mentha × piperita L. EO, known for its inhibitory activity against butyrylcholinesterase (BChE), an enzyme relevant to Alzheimer's disease, was chosen as a case study. The novel approach allowed for a comprehensive investigation by isolating the oxygenated fraction devoid of menthol. This facilitated a direct comparison of the biological activity of the whole EO against the total oxygenated fraction (from flash chromatography) and the menthol-devoid fraction (from prep-GC), as well as pure (-)-menthol, pure (-)-menthone, and their mixture.

SIGNIFICANCE: The results clearly indicate that (-)-menthol, (-)-menthone, and other terpenes within the oxygenated fraction jointly contribute to the overall BChE inhibitory activity. These findings highlight the complex interplay among Mentha × piperita L. EO constituents. Furthermore, this study underscores the potential of this new prep-GC technology for uncovering the biological roles of minor constituents in complex natural mixtures, by removing the contribution of the main representative components.},
}

*Oils, Volatile/chemistry/isolation & purification/pharmacology
Chromatography, Gas/methods
Butyrylcholinesterase/metabolism
Biological Assay
*Cholinesterase Inhibitors/chemistry/pharmacology/isolation & purification
Mentha piperita/chemistry

@article {pmid41544694,
year = {2026},
author = {van Rooij, JRA and van den Berg, M and Van Vosselen, M and Calus, E and Vasilkovska, T and Kosten, L and Van Spilbeeck, I and Van Audekerke, J and Van Dam, D and Bertoglio, D and Adhikari, MH and Verhoye, M},
title = {Long-term dietary interventions fail to mitigate functional connectivity loss and cognitive decline in the TgF344-AD rat model of Alzheimer's disease.},
journal = {Experimental neurology},
volume = {398},
number = {},
pages = {115647},
doi = {10.1016/j.expneurol.2026.115647},
pmid = {41544694},
issn = {1090-2430},
abstract = {Short-term caloric restriction (CR) and resveratrol (Rsv) supplementation have shown potential in preserving brain function in aging and neurodegenerative diseases such as AD. However, there is a lack of knowledge regarding the potential benefits of long-term CR or Rsv on brain health in context of AD. Therefore, we aimed to assess the effects of short-term (1 month) CR and Rsv administration on resting-state functional connectivity (rs-FC), as well as the effect of long-term (8 months) CR or Rsv supplementation on rs-FC, spatial memory, amyloid burden, and neuroinflammation in male and female TgF344-AD (Tg) and wild-type (WT) rats. In Tg rats, short-term CR decreased rs-FC in female rats, while long-term CR decreased rs-FC and modestly improved spatial memory in male rats. Long-term CR and Rsv altered regional amyloid burden, and CR decreased IBA-1 in males without affecting GFAP. Overall, long-term CR and Rsv failed to mitigate FC loss and cognition, underscoring the potentially limited impact of these dietary interventions in AD.},
}

@article {pmid41544692,
year = {2026},
author = {Gu, Y and Zhang, B and Lei, C and Guan, Y and Fan, B and Xu, W and Jin, A and Deng, Q and Xue, R and Yang, X and Zhu, X},
title = {The metabolic reprogramming of lactate in the nervous system.},
journal = {Experimental neurology},
volume = {398},
number = {},
pages = {115643},
doi = {10.1016/j.expneurol.2026.115643},
pmid = {41544692},
issn = {1090-2430},
abstract = {Lactate, a critical energetic substrate and signaling molecule in the central nervous system (CNS), plays a pivotal role in maintaining neurophysiological homeostasis and driving the pathogenesis of neurodegenerative disorders through metabolic reprogramming. Herein, this review systematically summarizes recent progress in molecular mechanisms governing lactate metabolic reprogramming as well as its multiple biological functions in the central nervous system. Under physiological conditions, lactate regulates energy distribution via the astrocyte-neuron lactate shuttle, while mediates neural communication through receptors including G Protein-Coupled Receptor 81 and N-Methyl-d-Aspartate Receptor, thereby modulating synaptic plasticity and memory consolidation. In neurodegenerative pathologies (such as Alzheimer's and Parkinson's diseases), dysregulated lactate reprogramming is observed in the form of dynamic lactate imbalance, altered expression of monocarboxylate transporters and lactate dehydrogenase, and defective mitochondrial energy coupling. These perturbations further enhance neuronal damage by triggering neuroinflammation and perturbing epigenomic homeostasis (e.g., histone lactylation). Critical knowledge gaps remain unresolved: (1) The temporal dynamics of lactate flux during disease progression remain uncharacterized; (2) The spatial heterogeneity of lactate distribution across brain nuclei and its regulatory mechanisms are debated; (3) Consensus is lacking regarding functional alterations of core lactate metabolic components; and (4) The precise signaling cascades through which lactate modulates neurodegeneration require elucidation. By integrating contemporary research on central nervous system lactate reprogramming, this work provides novel perspectives on neurodegenerative disease mechanisms and establishes a theoretical framework for developing targeted therapeutic strategies that modulate lactate metabolism.},
}

@article {pmid41544613,
year = {2026},
author = {Renna, M and Bonavita, R and Dixon, G and Verdicchio, LV and Fleming, A},
title = {The interplay between autophagy and unconventional secretion in neurodegeneration.},
journal = {Cell chemical biology},
volume = {33},
number = {1},
pages = {10-32},
doi = {10.1016/j.chembiol.2025.12.007},
pmid = {41544613},
issn = {2451-9448},
mesh = {*Autophagy ; Humans ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; alpha-Synuclein/metabolism ; tau Proteins/metabolism ; },
abstract = {Within neurons, the misfolding and aggregation of certain proteins has been identified as a common feature of many late-onset neurodegenerative diseases (NDs). These aggregate-prone proteins include tau (in both primary tauopathies and in Alzheimer's disease) and alpha-synuclein in Parkinson's disease. There is strong experimental evidence that the upregulation of intracellular clearance pathways (autophagy and ubiquitin-proteasome pathways) can clear aggregate-prone proteins in experimental models. When the flux through these pathways is increased, the levels of aggregate-prone proteins are reduced, resulting in improved cell survival in both cell-based and animal models of ND. More recently, a third strategy for clearing proteins from cells has been identified, via the unconventional secretion of proteins out of the cell. However, secretion may also facilitate the spreading and propagation of disease through a prion-like process. This review explains how the autophagy and unconventional secretion pathways interact and how these impact ND.},
}

*Autophagy
Humans
*Neurodegenerative Diseases/metabolism/pathology
Animals
alpha-Synuclein/metabolism
tau Proteins/metabolism

@article {pmid41544446,
year = {2026},
author = {Hodgins, ML and Maxwell, SP and Howlett, SE and Rockwood, K},
title = {Blood biomarkers of frailty and cognition: A scoping review.},
journal = {Neurobiology of aging},
volume = {161},
number = {},
pages = {14-30},
doi = {10.1016/j.neurobiolaging.2026.01.003},
pmid = {41544446},
issn = {1558-1497},
abstract = {Frailty increasingly is recognized as a factor that modifies the relationship between disease biomarkers, including neuropathology, and dementia expression. The mechanisms underlying the relationship between frailty and dementia remain unclear, but blood biomarkers can offer insight into these mechanisms. We completed a scoping review of research examining the associations between blood biomarkers, frailty, and cognition. Three online databases were searched to identify original research examining blood biomarkers in the context of frailty and/or cognitive decline that accounted for the other condition in the analysis through stratification or inclusion in the model. Five of the 76 unique biomarkers identified -A disintegrin and Metalloproteinase 10 (ADAM10), fibrinogen, interleukin (IL)-6, neurofilament light chain (NfL) and vitamin D- were significantly and independently associated with both frailty and cognition. All five biomarkers could contribute to aging mechanisms, including disrupted proteostasis, chronic inflammation, dysregulated metabolism and/or deregulated nutrient sensing. These biomarkers could thus be common pathways of frailty and cognitive decline. Despite the Alzheimer-defining roles of β-amyloid and phosphorylated tau, these biomarkers typically are reported without considering the degree of frailty. Future biomarker research in cognitive decline and frailty should seek a clearer understanding of their relationship.},
}

@article {pmid41544372,
year = {2026},
author = {Rosenberg, A and Solomon, A and Bonnard, A and Daniilidou, M and Hagman, G and Hall, A and Matton, A and Öhlund-Wistbacka, U and Westman, E and Kivipelto, M},
title = {Preparing for the implementation of anti-amyloid therapies in Europe: Assessing real-world eligibility for lecanemab and donanemab in a Swedish memory clinic.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {3},
pages = {100476},
doi = {10.1016/j.tjpad.2025.100476},
pmid = {41544372},
issn = {2426-0266},
abstract = {Lecanemab and donanemab are the first anti-Aβ treatments to receive approval in Europe. Eligibility criteria are strict, eg., APOE ε4/4 carriers are excluded. Successful implementation in public healthcare hinges on accurate estimates of eligibility rates in settings which will be the first to roll out the treatments (specialized memory clinics with early disease stages). We applied the appropriate use recommendations (AUR) to assess treatment eligibility in a Swedish tertiary memory clinic where Aβ and APOE assessments are routinely performed. Of the full cohort (N = 410), 26 and 25 patients met the AUR criteria for lecanemab and donanemab, respectively (6 %; partial overlap between the groups). After excluding APOE ε4/4 carriers in line with the European guidelines, only 14 and 13 patients remained eligible (3 %). In clinics with younger populations, a significant percentage of potentially eligible patients are likely to have the APOE ε4/4 genotype. These findings are important to inform the implementation of anti-Aβ treatments.},
}

@article {pmid41544353,
year = {2026},
author = {Li, Z and Han, R and Fan, Y and Wang, Z and Wang, H and Jiang, D and He, X and Xiang, J and Yu, H and Huang, S},
title = {Interaction effects of extreme temperature events and air pollutants on neurodegenerative disease mortality: A case-crossover study in a cold-winter, hot-summer region of China.},
journal = {Ecotoxicology and environmental safety},
volume = {309},
number = {},
pages = {119732},
doi = {10.1016/j.ecoenv.2026.119732},
pmid = {41544353},
issn = {1090-2414},
abstract = {Extreme temperature events (ETEs) and air pollutants are both linked to neurodegenerative diseases, yet their interactions remain underexplored. This case-crossover study examined the effects of ETEs and six ambient air pollutants (PM10, PM2.5, O3, SO2, NO2, and CO) on mortality due to neurodegenerative diseases in a cold-winter, hot-summer region of China (2014-2021). Using a conditional logistic regression model combined with a distributed lag non-linear model, we found that heat wave and cold spell significantly increased overall neurodegenerative disease mortality, with peak effects at lag 0-14 days for heat wave (OR=1.77[95 %CI: 1.58, 1.98]) and lag 0-8 days for cold spell (OR=1.25[95 %CI: 1.10, 1.42]). All six air pollutants were significantly associated with mortality during the warm season, with PM2.5 and SO2 posing higher risks. Positive interactions were observed between heat wave and four air pollutants (PM10, PM2.5, SO2, CO), particularly with SO2 (interaction OR = 1.84[95 %CI: 1.68, 2.01]). The strongest interaction effects were found for Alzheimer's disease mortality across all subcategories. Vulnerable groups included females, individuals aged > 80 years, and those without a spouse. These findings highlight the compounded risks of ETEs and air pollution on neurodegenerative disease mortality, emphasizing the need for synergistic warning systems and targeted control measures. SYNOPSIS: This study provides evidence for the interaction between short-term exposure to extreme temperature events and air pollutants on neurodegenerative disease mortality.},
}

@article {pmid41544088,
year = {2026},
author = {Oludiran, A and Lewis, B and Pudwill, C and Chukkapalli, S and Ahmadi, H and Bannova, D and Linares, A and Burks, J and Hillman, JD and Dunn, WA and Progulske-Fox, A},
title = {Investigation of a viable but non-culturable state in Porphyromonas gingivalis and host cell invasion.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0340605},
pmid = {41544088},
issn = {1932-6203},
mesh = {*Porphyromonas gingivalis/pathogenicity/physiology/drug effects/growth & development ; Humans ; *Microbial Viability/drug effects ; Hydrogen Peroxide/pharmacology ; Oxidative Stress/drug effects ; Endothelial Cells/microbiology ; Biofilms ; },
abstract = {Porphyromonas gingivalis (P. gingivalis) is a gram-negative, black-pigmented, anaerobic pathogen known for its biofilm formation and its central role in periodontal disease. More recently, P. gingivalis has been implicated in various systemic conditions, including atherosclerosis, Alzheimer's disease, and certain types of cancer, such as pancreatic and oral cancer. This bacterium employs several mechanisms to evade environmental stress, thereby contributing to its pathogenicity. The viable but non-culturable (VBNC) state is characterized by bacteria that remain viable but have reduced metabolic activity and are unable to form colonies on conventional culture media. To induce the VBNC state in P. gingivalis, we subjected the bacterium to oxidative stress using H2O2 and subsequently resuscitated it from this state with sodium pyruvate. We utilized viability staining, confocal microscopy, and flow cytometry (FC) to count live and dead bacteria, confirming the presence of significant numbers of viable P. gingivalis cells both before and after stress induction. Despite being viable, the stressed P. gingivalis failed to form colonies on blood agar plates after seven days of incubation, indicating it had entered the VBNC state. We were then able to resuscitate the VBNC P. gingivalis by adding sodium pyruvate, and the growth of the resuscitated bacteria on plates was comparable to that of control P. gingivalis. Investigation into the invasiveness of P. gingivalis in the VBNC state was conducted using human coronary artery endothelial cells (HCAECs). P. gingivalis in the VBNC state demonstrated the ability to invade and based on live/dead staining, showed that a substantial proportion of the VBNC P. gingivalis remained viable within the host cells for extended periods. In this study, we explore the VBNC survival strategy previously described in many aerobic bacteria but not previously reported in anaerobes such as P. gingivalis. The objectives of this study are to verify the VBNC state in P. gingivalis, determine whether this state can be reversed and assess the extent to which it impacts the ability of P. gingivalis to invade host cells. Understanding the VBNC and resuscitation states will be instrumental in guiding the development of more effective therapies for periodontitis and other diseases associated with P. gingivalis infection.},
}

*Porphyromonas gingivalis/pathogenicity/physiology/drug effects/growth & development
Humans
*Microbial Viability/drug effects
Hydrogen Peroxide/pharmacology
Oxidative Stress/drug effects
Endothelial Cells/microbiology
Biofilms

@article {pmid41544026,
year = {2026},
author = {Zahedipour, M and Saniee Abadeh, M and Shojaei, S},
title = {Alzheimer's disease prediction via an explainable CNN using genetic algorithm and SHAP values.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0337800},
pmid = {41544026},
issn = {1932-6203},
mesh = {*Alzheimer Disease/diagnostic imaging/diagnosis ; Humans ; *Algorithms ; Magnetic Resonance Imaging/methods ; *Neural Networks, Computer ; Brain/diagnostic imaging ; Aged ; Male ; Female ; Genetic Algorithms ; },
abstract = {Convolutional neural networks (CNNs) are widely recognized for their high precision in image classification. Nevertheless, the lack of transparency in these black-box models raises concerns in sensitive domains such as healthcare, where understanding the knowledge acquired to derive outcomes can be challenging. To address this concern, several strategies within the field of explainable AI (XAI) have been developed to enhance model interpretability. This study introduces a novel XAI technique, GASHAP, which integrates a genetic algorithm (GA) with SHapley Additive exPlanations (SHAP) to improve the explainability of our 3D convolutional neural network (3D-CNN) model. The model is designed to classify magnetic resonance imaging (MRI) brain scans of individuals with Alzheimer's disease and cognitively normal controls. Deep SHAP, a widely used XAI technique, facilitates the understanding of the influence exerted by various voxels on the final classification outcome (Lundberg SM, Lee SI. A unified approach to interpreting model predictions. In: Advances in Neural Information Processing Systems, 2017. 4765-74. https://doi.org/10.5555/3295222.3295230). However, voxel-level representation alone lacks interpretive clarity. Therefore, the objective of this study is to provide findings at the level of anatomically defined brain regions. Critical regions are identified by leveraging their SHAP values, followed by the application of a genetic algorithm to generate a definitive mask highlighting the most significant regions for Alzheimer's disease diagnosis (Shahamat H, Saniee Abadeh M. Brain MRI analysis using a deep learning based evolutionary approach. Neural Netw. 2020;126:218-34. https://doi.org/10.1016/j.neunet.2020.03.017 PMID: 32259762). The research commenced by implementing a 3D-CNN for MRI image classification. Subsequently, the GASHAP technique was applied to enhance model transparency. The final result is a brain mask that delineates the pertinent regions crucial for Alzheimer's disease diagnosis. Finally, a comparative analysis is conducted between our findings and those of previous studies.},
}

*Alzheimer Disease/diagnostic imaging/diagnosis
Humans
*Algorithms
Magnetic Resonance Imaging/methods
*Neural Networks, Computer
Brain/diagnostic imaging
Aged
Male
Female
Genetic Algorithms

@article {pmid41543852,
year = {2026},
author = {Yu, L and Wang, T and Du, L and Bennett, DA and Schneider, JA and Boyle, PA},
title = {Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults.},
journal = {JAMA network open},
volume = {9},
number = {1},
pages = {e2554354},
pmid = {41543852},
issn = {2574-3805},
mesh = {Humans ; Female ; Male ; Aged ; Aged, 80 and over ; *Independent Living ; Alzheimer Disease/pathology ; *Brain/pathology ; *Aging/pathology ; *Cognition/physiology ; Cohort Studies ; *Cognitive Dysfunction/pathology ; },
abstract = {IMPORTANCE: Mixed neuropathologies are common, and yet the full extent to which these pathologies coexist is not entirely clear.

OBJECTIVES: This study aims to identify distinct neuropathologic profiles in community-dwelling older adults and to examine associated cognitive trajectories over time.

This study included participants in 2 community-based cohort studies of aging and dementia. Participants were older adults without known dementia at enrollment who agreed to annual evaluations and brain donation. The Religious Orders Study started in 1994, and the Rush Memory and Aging Project started in 1997. Both studies are ongoing. Data were analyzed in May 2025.

EXPOSURES: Annual uniform detailed evaluations for up to 30 years and brain autopsy and neuropathologic evaluation after death.

MAIN OUTCOMES AND MEASURES: Neuropathologic evaluations assessed Alzheimer disease neuropathologic change (ADNC), Lewy bodies, limbic-predominant age-related transactive response DNA-binding protein 43 kDa encephalopathy neuropathologic change (LATE-NC), hippocampal sclerosis, infarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis. Annual cognitive scores were derived from a battery of 19 tests that assessed multiple cognitive domains. Latent neuropathologic profiles were identified using hierarchical clustering, and longitudinal cognitive trajectories associated with each profile were estimated using functional mixed-effects models.

RESULTS: A total of 1633 older adults were included in the study. The mean (SD) age at death was 90.4 (6.4) years, 1156 (70.8%) were female, and the mean (SD) years of education was 16.2 (3.6) years. A total of 46 participants (2.8%) self-reported as Black, 42 (2.6%) as Hispanic, and 1579 (96.6%) as White. More than 80% of individuals had mixed neuropathologies at autopsy, and 280 unique combinations of copathologies were identified. Hierarchical clustering revealed 5 distinct neuropathologic profiles: profile 1 (259 participants [15.9%]) was characterized by a high burden of infarcts and vessel diseases, profile 2 (201 participants [12.3%]) by high LATE-NC and hippocampal sclerosis, profile 3 (355 participants [21.7%]) by high Lewy bodies, profile 4 (159 participants [9.7%]) by high ADNC and amyloid angiopathy, and profile 5 (659 participants [40.4%]) by low pathology overall. Cognitive trajectories differed across profiles in terms of both the rate of decline and the timing of the onset of decline with fastest decline observed for profile 2 and 4.

CONCLUSIONS AND RELEVANCE: In this cohort study, mixed neuropathologies were extremely common and complex. Compared with vascular conditions, degenerative pathologies clustered into distinct profiles. Profiles characterized by high burdens of ADNC and separately, LATE-NC and hippocampal sclerosis, had the most potent associations with cognitive decline.},
}

Humans
Female
Male
Aged
Aged, 80 and over
*Independent Living
Alzheimer Disease/pathology
*Brain/pathology
*Aging/pathology
*Cognition/physiology
Cohort Studies
*Cognitive Dysfunction/pathology

@article {pmid41543797,
year = {2026},
author = {Konat, GW},
title = {Dysfunctional respiration as a risk factor for Alzheimer disease: a hypothesis.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {21},
pmid = {41543797},
issn = {1573-7365},
}

@article {pmid41543776,
year = {2026},
author = {Li, X and Zhang, L and Xia, J and Zheng, M and Zhou, Z and Cai, J},
title = {Multi-omics Mendelian randomization and machine learning identify candidate therapeutic targets for Alzheimer's and Parkinson's diseases.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {37},
number = {1},
pages = {24},
pmid = {41543776},
issn = {1432-1777},
support = {82474605//National Natural Science Foundation of China/ ; XJG20230163//Natural Science Foundation of Fujian/ ; },
mesh = {*Machine Learning ; *Parkinson Disease/genetics/drug therapy ; Animals ; *Alzheimer Disease/genetics/drug therapy ; *Mendelian Randomization Analysis ; Humans ; Mice ; Genome-Wide Association Study ; Quantitative Trait Loci ; Disease Models, Animal ; Molecular Docking Simulation ; Transcriptome ; Multiomics ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are major public health challenges lacking effective therapies. To identify potential drug targets, we integrated large-scale genome-wide association studies with expression, methylation, protein, and splicing QTL datasets using Mendelian Randomization (MR) and summary-data-based MR (SMR). Colocalization analysis and machine learning were applied to prioritize candidate genes, followed by in silico druggability evaluation through molecular docking and molecular dynamics (MD) simulations. In animal models, candidate genes identified by transcriptomic analysis were further validated using integrative molecular and functional experiments. We identified several genes with potential causal links to AD (e.g., IQCE, HDHD2, ALPP) and PD (e.g., IL15, STK3, CHRNB1). Transcriptomic analyses indicated a consistent downregulation of IL-15 in PD model mice, corroborated by subsequent Western blot and immunohistochemical validation. Among predicted compounds, Prednisolone (ALPP), Sirolimus (IL15), and CHEMBL379975 (STK3) showed favorable binding affinities and stable MD trajectories, suggesting promising therapeutic relevance. Collectively, these findings highlight 12 QTL-regulated genes as promising molecular targets for further investigation in the context of NDDs. While the computational results provide a useful basis for hypothesis generation, experimental validation will be essential to determine the biological relevance and therapeutic potential of these candidate genes and compounds.},
}

*Machine Learning
*Parkinson Disease/genetics/drug therapy
Animals
*Alzheimer Disease/genetics/drug therapy
*Mendelian Randomization Analysis
Humans
Mice
Genome-Wide Association Study
Quantitative Trait Loci
Disease Models, Animal
Molecular Docking Simulation
Transcriptome
Multiomics

@article {pmid41543642,
year = {2026},
author = {Blandi, L and Del Riccio, M},
title = {From breath to brain: influenza vaccination as a pragmatic strategy for dementia prevention.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-026-03323-5},
pmid = {41543642},
issn = {1720-8319},
abstract = {Aging populations require scalable strategies to delay or prevent dementia. Beyond the prevention of neurological injury associated with seasonal influenza, vaccination may help mitigate vascular and neuroinflammatory injury underlying cognitive impairment. Influenza infection can cause a marked short‑term increase in myocardial infarction risk, and acute infections have also been associated with transient increases in stroke risk. Experimental models show prolonged microglial activation and synaptic loss even from non-neurotropic strains - processes likely modulated by vaccination. Epidemiologic data consistently support this evidence; a 2023 meta-analysis, including observational studies, of ~ 2.09 million adults identified a 31% lower risk of incident dementia; US matched cohorts demonstrated 40% lower risk of Alzheimer's disease (absolute decrease 3.4%); Veterans Health data showed a 0.86 hazard ratio for dementia; and UK Biobank data showed lower risk for all-cause (0.83 h), and vascular dementia (0.58 h) with a dose-response association by vaccination term. Randomized trials suggest fewer adverse cardiovascular events in vaccine recipients giving even more biological plausibility to this concept. Despite that, prevention through influenza vaccination is not fully realized in older adults due to low levels of perceived risk, vaccine confidence, and variations in clinical practice guidance. This public health perspective reviews the physiopathological and epidemiological evidence in support of influenza vaccination as a pragmatic, dementia risk-modifying intervention within healthy aging strategies and encourages the inclusion of vaccination status in hospital discharge and chronic-care pathways, integration of cognitive outcomes in monitoring, and equity-centered research to eliminate barriers to behavioral and implementation.},
}

@article {pmid41543510,
year = {2026},
author = {Dumoulin, D and Ghrayeb, M and Côté, S and Garneau, D and Chai, L and Frost, EH and Fülöp, T and Beauregard, PB},
title = {Bidirectional relationship between the biofilm of Porphyromonas gingivalis and the amyloid-beta peptide.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0198125},
doi = {10.1128/spectrum.01981-25},
pmid = {41543510},
issn = {2165-0497},
abstract = {UNLABELLED: Periodontitis and Porphyromonas gingivalis infections are significant risk factors for the onset of Alzheimer's disease (AD). Despite the reliance of P. gingivalis on its biofilm for its survival and virulence, the impact of the extracellular matrix on AD's neuropathological hallmarks has never been examined. In this study, we report a bidirectional relationship between the amyloid-beta (Aβ) peptide, which plays a central role in AD, and the biofilm of P. gingivalis. Using multiple fluorescent markers for biofilm components, we observed that Aβ1-40 inhibited biofilm formation while Aβ1-42 increased extracellular matrix production. Also, using thioflavin T staining and atomic force microscopy, we observed co-aggregation of the biofilm and monomeric Aβ1-40, resulting in faster aggregation and significant changes in aggregate structure. Our findings propose mechanistic explanations for the role of P. gingivalis as a risk factor for AD and offer potential mechanisms for microbial involvement in AD etiology.

IMPORTANCE: While the etiology of Alzheimer's disease has been studied extensively for the past 50 years, its exact causes remain unknown. Our current understanding is that the accumulation of multiple genetic and environmental risk factors would lead to the onset of the disease. Porphyromonas gingivalis is a bacterium that produces biofilm and elicits periodontitis, a chronic infection of the gums that constitutes a risk factor for Alzheimer's disease. While studies have looked at the effects of P. gingivalis in triggering Alzheimer's symptoms in animal models, none have explored the impact of the biofilm, which is essential in this bacterium. Our study seeks to bridge that gap by demonstrating a bidirectional relationship between P. gingivalis biofilm and amyloid beta, one of the brain lesions involved in Alzheimer's disease. By understanding the risk factors involved in Alzheimer's disease and their impact, we aim to provide valuable insights on prevention and treatment.},
}

@article {pmid41543367,
year = {2026},
author = {Bhagunde, P and Penner, N and Willis, BA and Bell, R and Charil, A and Irizarry, MC and Hersch, S and Reyderman, L},
title = {Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR-SB Utilizing Semi-Mechanistic Model.},
journal = {CPT: pharmacometrics & systems pharmacology},
volume = {15},
number = {2},
pages = {e70173},
doi = {10.1002/psp4.70173},
pmid = {41543367},
issn = {2163-8306},
mesh = {Humans ; *Alzheimer Disease/drug therapy/diagnostic imaging/metabolism ; Positron-Emission Tomography ; Disease Progression ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage/pharmacology ; *Plaque, Amyloid/drug therapy/diagnostic imaging/metabolism ; Amyloid beta-Peptides/metabolism ; *Brain/metabolism/diagnostic imaging/drug effects ; Male ; Aged ; Female ; Double-Blind Method ; Models, Biological ; },
abstract = {Lecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to protofibrils of amyloid-beta (Aβ) protein. In clinical studies, lecanemab has been shown to reduce amyloid markers in early symptomatic Alzheimer's disease and slow decline on clinical endpoints of cognition and function. Nonlinear mixed-effects modeling assessed the correlation between amyloid PET and change in CDR-SB using data from lecanemab phase 2 study (Study 201) and phase 3 study (Study 301; Clarity AD). Data from placebo-treated subjects were used to establish a disease-progression model; the effect of amyloid reduction on disease progression was defined using data from lecanemab-treated subjects. CDR-SB scores were used with beta regression to fit a Richard's function parameterized in terms of baseline CDR-SB, intrinsic rate of disease progression, shape, and precision of the beta distribution. Simulations were conducted to evaluate the impact of lecanemab treatment over 4 years. Baseline CDR-SB was predicted by diagnosis and baseline mini-mental state examination (BMMSE) score. Intrinsic rate of disease progression was predicted by amyloid PET and BMMSE. Amyloid PET was a better predictor of drug effect than lecanemab exposure, demonstrating amyloid reduction as a surrogate marker of efficacy. Simulations projected the difference in CDR-SB between lecanemab and placebo treated subjects continued increasing over 4 years. Patients with low baseline amyloid and less severe disease were projected to have slower disease progression and better outcomes with lecanemab treatment.},
}

Humans
*Alzheimer Disease/drug therapy/diagnostic imaging/metabolism
Positron-Emission Tomography
Disease Progression
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage/pharmacology
*Plaque, Amyloid/drug therapy/diagnostic imaging/metabolism
Amyloid beta-Peptides/metabolism
*Brain/metabolism/diagnostic imaging/drug effects
Male
Aged
Female
Double-Blind Method
Models, Biological

@article {pmid41543365,
year = {2026},
author = {Thomas, V and Zurzolo, C},
title = {Organelle dysfunction and TNT-mediated aggregate spreading in neurodegeneration.},
journal = {Physiology (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1152/physiol.00048.2025},
pmid = {41543365},
issn = {1548-9221},
support = {AAP 2024//FONDATION ALZHEIMER (The Alzheimer's Foundation)/ ; AAP 2021//Association France Parkinson (France Parkinson)/ ; AAP PFA 2021 #6156//Association France Alzheimer (French Alzheimer's Association)/ ; ANR-23-CE16-0012-03//Agence Nationale de la Recherche (ANR)/ ; FRM MND202310017892//Fondation pour la Recherche Médicale (FRM)/ ; //French Ministry of Research/ ; },
abstract = {Organelle dysfunction is a central hallmark of neurodegenerative diseases (NDs), which are characterized by the pathological accumulation of misfolded proteins capable of inducing aggregation in healthy cells. This process generates a self-perpetuating cycle of protein misfolding and spreading across interconnected neuronal networks. In this review, we provide an integrated overview of organelle alterations associated with major NDs, emphasizing the pivotal roles of lysosomes, mitochondria, and the endoplasmic reticulum (ER) at the crossroads of proteostasis, metabolism, and stress signaling. We examine how defects in these organelles create conditions that favor aggregate formation and cellular vulnerability, with a focus on α-synuclein and Tau, the main aggregating proteins in Parkinson's and Alzheimer's diseases, respectively. We then explore mechanisms of intercellular protein transfer, highlighting the emerging role of tunneling nanotubes (TNTs). We discuss how organelle status influences TNT formation and cargo selection, and how TNTs may act as conduits for the propagation of pathogenic aggregates. Finally, we summarize the downstream consequences of TNT-mediated transfer in recipient cells, including alterations in the autophagy-lysosomal pathway, TFEB-dependent transcription, mitochondrial stress responses, calcium homeostasis, and inflammatory or senescent signaling. Together, these insights underscore the intertwined roles of organelle dysfunction and TNT-mediated communication in driving the progression of NDs and suggest new therapeutic avenues aimed at restoring organelle function and limiting aggregate spread.},
}

@article {pmid41543363,
year = {2026},
author = {Beers, S and de Groot, LCPGM and van Loenen, MR and Remie, LB and Bromhaar, MG and Anesi, A and Vrhovsek, U and Oosterman, JM and Aarts, E and van Trijp, MPH and Vermeiren, Y},
title = {Association Between the Dutch Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND-NL) Diet Adherence and Systemic Tryptophan Metabolites in Older Adults at Risk of Cognitive Decline: An Exploratory Study.},
journal = {Molecular nutrition & food research},
volume = {70},
number = {1},
pages = {e70377},
pmid = {41543363},
issn = {1613-4133},
support = {/NWO_/Dutch Research Council/Netherlands ; },
mesh = {Humans ; *Tryptophan/blood/metabolism ; *Diet, Mediterranean ; Male ; Female ; Aged ; *Cognitive Dysfunction/blood/prevention & control/diet therapy ; *Dietary Approaches To Stop Hypertension ; Kynurenine/blood ; Middle Aged ; Netherlands ; Neurodegenerative Diseases/diet therapy ; Patient Compliance ; },
abstract = {Tryptophan (TRP) metabolism is emerging as a focus of investigation in Alzheimer's disease research. In addition, diet might impact TRP's metabolic fate. The aim of this study was to explore the association between adherence to the Dutch Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND-NL) diet and systemic TRP metabolite levels and their related ratios in older adults at risk of cognitive decline. Data of the HELI multidomain lifestyle intervention study (n = 82) were used. Dietary intake data (FFQ) and fasted plasma levels were collected at baseline and 26 weeks follow-up. Bivariate Latent Change Score Models (LCSMs) were applied to assess both level-level and change-change associations, adjusted for lifestyle factors. Changes in MIND-NL diet adherence were significantly inversely associated with changes in the kynurenine:large neutral amino acids ratio (path coefficient -0.457, SE:0.206, p = 0.03) and kynurenine:tryptophan ratio (path coefficient -0.558 SE:0.235, p = 0.02). In addition, MIND-NL diet adherence was associated with lower levels of the neurotoxic metabolite quinolinic acid (path coefficient -0.186, SE:0.0700, p = 0.008), but within the crude model only. Our findings suggest that greater adherence to the MIND-NL diet may contribute to decreased activation of the kynurenine pathway.},
}

Humans
*Tryptophan/blood/metabolism
*Diet, Mediterranean
Male
Female
Aged
*Cognitive Dysfunction/blood/prevention & control/diet therapy
*Dietary Approaches To Stop Hypertension
Kynurenine/blood
Middle Aged
Netherlands
Neurodegenerative Diseases/diet therapy
Patient Compliance

@article {pmid41542929,
year = {2026},
author = {Durant, A and Mukherjee, S and Lee, ML and Choi, SE and Scollard, P and Klinedinst, BS and Trittschuh, EH and Mez, J and Farrer, LA and Gifford, KA and Cruchaga, C and Hassenstab, J and Naj, AC and Wang, LS and Johnson, SC and Engelman, CD and Kukull, WA and Keene, CD and Saykin, AJ and Cuccaro, ML and Kunkle, BW and Pericak-Vance, MA and Martin, ER and Bennett, DA and Barnes, LL and Schneider, JA and Bush, WS and Haines, JL and Mayeux, R and Vardarajan, BN and Albert, MS and Thompson, PM and Jefferson, AL and , and Crane, PK and Dumitrescu, L and Archer, DB and Hohman, TJ and Gaynor, LS},
title = {Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71024},
pmid = {41542929},
issn = {1552-5279},
support = {//The ADSP Phenotype Harmonization Consortium/ ; U24 AG074855/AG/NIA NIH HHS/United States ; U01 AG068057/AG/NIA NIH HHS/United States ; R01 AG059716/AG/NIA NIH HHS/United States ; K01 AG073584/AG/NIA NIH HHS/United States ; K24 AG046373/AG/NIA NIH HHS/United States ; U19 AG066567/AG/NIA NIH HHS/United States ; R01 AG021155/AG/NIA NIH HHS/United States ; R01 AG0271761//the Wisconsin Registry for Alzheimer's Prevention/ ; R01 AG037639/AG/NIA NIH HHS/United States ; R01 AG054047/AG/NIA NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; W81XWH-12-2-0012//the Alzheimer's Disease Neuroimaging Initiative/ ; //the National Institute on Aging/ ; //the National Institute of Biomedical Imaging and Bioengineering/ ; //following: AbbVie/ ; /ALZ/Alzheimer's Association/United States ; //Alzheimer's Drug Discovery Foundation/ ; //Araclon Biotech/ ; //BioClinica, Inc./ ; //Biogen/ ; //Bristol-Myers Squibb Company/ ; //CereSpir, Inc./ ; //Cogstate/ ; //Elan Pharmaceuticals, Inc./ ; //Eli Lilly and Company/ ; //EuroImmun/ ; //F. Hoffmann-La Roche Ltd./ ; //Genentech, Inc./ ; //Fujirebio/ ; //GE Healthcare/ ; //IXICO Ltd./ ; //Janssen Alzheimer Immunotherapy Research & Development, LLC./ ; //Johnson & Johnson Pharmaceutical Research & Development LLC/ ; //Lumosity/ ; //Lundbeck/ ; //Meso Scale Diagnostics, LLC./ ; //NeuroRx Research/ ; //Neurotrack Technologies/ ; //Novartis Pharmaceuticals Corporation/ ; //Pfizer Inc./ ; //Piramal Imaging/ ; //Servier/ ; //Takeda Pharmaceutical Company/ ; //Transition Therapeutics/ ; /CAPMC/CIHR/Canada ; /NH/NIH HHS/United States ; //Northern California Institute for Research and Education/ ; //Alzheimer's Therapeutic Research Institute/ ; //Laboratory for Neuro Imaging/ ; R01 AG017917/AG/NIA NIH HHS/United States ; P30 AG10161//University of Southern California/ ; P30 AG072975/AG/NIA NIH HHS/United States ; R01 AG022018/AG/NIA NIH HHS/United States ; R01 AG056405/AG/NIA NIH HHS/United States ; UH2 NS100599/NS/NINDS NIH HHS/United States ; UH3 NS100599/NS/NINDS NIH HHS/United States ; R01 AG064233/AG/NIA NIH HHS/United States ; R01 AG15819//University of Southern California/ ; R01 AG067482/AG/NIA NIH HHS/United States ; //Illinois Department of Public Health/ ; U24 AG072122/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Aged, 80 and over ; Genotype ; White People/genetics ; *Apolipoproteins E/genetics ; Black or African American/genetics ; Gene Frequency ; *Alzheimer Disease/genetics ; Alleles ; *Cognition/physiology ; Executive Function/physiology ; Aged ; Apolipoprotein E4/genetics ; Neuropsychological Tests ; White ; },
abstract = {INTRODUCTION: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined apolipoprotein E (APOE) allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer's disease dementia cases.

METHODS: In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins.

RESULTS: NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles and higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance.

DISCUSSION: We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring cognitive resilience differ across race groups.

HIGHLIGHTS: Apolipoprotein E (APOE) allele frequency differs between SuperAgers and cases APOE allele frequency differs between non-Hispanic White SuperAgers and controls The relationship of APOE and non-Hispanic Black SuperAger status is unclear.},
}

Humans
Male
Female
Aged, 80 and over
Genotype
White People/genetics
*Apolipoproteins E/genetics
Black or African American/genetics
Gene Frequency
*Alzheimer Disease/genetics
Alleles
*Cognition/physiology
Executive Function/physiology
Aged
Apolipoprotein E4/genetics
Neuropsychological Tests
White

@article {pmid41542848,
year = {2026},
author = {Dewitte, L and Cheung, SC and Foxe, D and Ahmed, RM and Piguet, O and Irish, M},
title = {Understanding the multifaceted nature of quality of life in dementia using a transdiagnostic network analysis approach.},
journal = {Aging & mental health},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/13607863.2025.2610669},
pmid = {41542848},
issn = {1364-6915},
abstract = {OBJECTIVES: Efforts to improve quality of life (QOL) in dementia depend on its accurate conceptualization and assessment. We employed a data-driven network approach to examine the structure of relationships between individual QOL items. This approach allowed us to capture the complexity and multidimensional nature of QOL from the perspective of the person with dementia and their carer.

METHOD: Participants with dementia (n = 128) and carers completed the Quality of Life in Alzheimer's Disease questionnaire (QOL-AD), and measures of depressive symptoms, cognition, and functional abilities of the person with dementia, and carer burden. Gaussian graphical models with regularized partial correlations of QOL-AD items were estimated and compared, and item communities were detected.

RESULTS: Central elements that emerged in both self and carer-reported networks included Ability to do Things for Fun, Energy, and Life as a Whole. Memory and Money were less central. Distinct differences were also evident between self- and carer-networks. Whilst Self as a Whole was relatively more central in the self-reported network, Ability to Do Chores and Family were more central in the carer-reported network. Moreover, different communities were detected in the networks, corresponding to domains including socioeconomic, daily, self-referential, and instrumental functioning, with differential correlations to key clinical outcome variables.

CONCLUSION: QOL in dementia is inherently multidimensional and differs when assessed from the viewpoint of the person living with dementia versus their carer. Network approaches offer the granularity required to ensure that targeted interventions can be tailored toward these complementary perspectives.},
}

@article {pmid41542685,
year = {2026},
author = {Chea, EF},
title = {ATN Classification and Machine-Learned Plasma Biomarker Phenotypes Reveal Distinct Alzheimer's Pathology in a Population-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.02.26343331},
pmid = {41542685},
abstract = {BACKGROUND: The ATN (Amyloid/Tau/Neurodegeneration) framework provides a theory-driven approach to Alzheimer's disease (AD) classification using binary biomarker cutoffs, while unsupervised machine learning offers data-driven phenotyping. The concordance between these approaches in population-representative samples remains incompletely characterized.

OBJECTIVE: To compare plasma ATN classification with data-driven clustering methods and evaluate their associations with cognitive outcomes in a nationally representative cohort.

METHODS: We analyzed plasma biomarkers (Aβ42/40 ratio, p-tau181, NfL, GFAP) from 4,465 participants aged ≥51 years in the Health and Retirement Study 2016 Venous Blood Study. ATN profiles were classified using literature-based cutoffs. We applied k-means clustering, Gaussian mixture modeling, and variational autoencoder (VAE) dimensionality reduction to identify data-driven biomarker phenotypes. Agreement between ATN and clustering was quantified using adjusted Rand index (ARI) and normalized mutual information (NMI). Longitudinal analyses examined associations with cognitive decline over 4 years (2016-2020).

RESULTS: The analytic sample included 4,465 individuals (mean age 69.7±10.4 years; 58.7% female; 75.8% non-Hispanic White). ATN classification yielded 14 profiles, with A+/T-/N- (27.4%) and A-/T-/N-(22.6%) most prevalent. K-means clustering identified 4 optimal clusters with distinct biomarker signatures. Agreement between ATN and clusters was modest (ARI=0.119, NMI=0.113). Sensitivity analysis excluding GFAP from clustering improved agreement to ARI=0.187 (+57% relative increase), indicating that GFAP's orthogonal biological information accounts for approximately one-third of discordance, while binary categorization versus continuous phenotyping accounts for two-thirds.[Table S12] Additional sensitivity analyses confirmed that k=4 provides superior biological resolution over k=3 by preserving extreme phenotypes,[Table S13] and that Cluster 4 represents a stable biological structure across distance metrics[Table S14] despite its small size. Cluster 1 (n=51, 1.2%) showed severe pathology; Cluster 3 (n=3,479, 78.6%) represented the largest and most heterogeneous group, encompassing the broad spectrum of minimal to moderate pathology across all ATN profiles; Cluster 4 (n=14, 0.3%) exhibited a non-AD neurodegeneration pattern with high stability (Jaccard=0.779). VAE revealed localized nonlinear structure, though PCA achieved higher global separation (silhouette: PCA=0.671 vs VAE=0.564). Both ATN and clusters predicted 4-year cognitive decline (ATN R [2] =0.024, p<0.001; Clusters R [2] =0.019, p<0.001).

CONCLUSIONS: Theory-driven ATN classification and data-driven biomarker phenotyping capture partially overlapping but largely distinct biological information. Modest concordance (ARI=0.119) reflects three primary factors: binary cutoffs discarding continuous information (dominant), GFAP's orthogonal inflammatory signature (contributing ~one-third), and fundamental differences in biological constructs targeted. Sensitivity analyses confirmed that k=4 provides superior biological resolution over k=3, and that rare Cluster 4 represents a stable non-AD phenotype. Both approaches predict cognitive decline with modest effect sizes (R [2] =1.9-2.4%) consistent with population-based studies. Integrating theory-driven and data-driven frameworks promises a more comprehensive characterization of AD-related pathology in population research.},
}

@article {pmid41542678,
year = {2026},
author = {Nashiro, K and Min, J and Yoo, HJ and Cho, C and Dahl, MJ and Choi, P and J Lee, HR and Choupan, J and Mercer, N and Nasseri, P and Kim, AJ and Alemu, K and Rose, NF and Herrera, AY and Custer, R and Werkle-Bergner, M and Thayer, JF and Sordo, L and Head, E and Mather, M},
title = {Testing effects of paced breathing on plasma Aβ and brain perivascular spaces.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.08.26343624},
pmid = {41542678},
abstract = {UNLABELLED: Aging is the strongest known risk factor for Alzheimer's disease (AD), and elevated plasma amyloid-β (Aβ) levels in healthy adults are associated with increased AD risk. Aging is also associated with autonomic imbalance, characterized by increased sympathetic and decreased parasympathetic activity. In our previous randomized clinical trial, we found that four weeks of daily slow-paced breathing designed to enhance parasympathetic activity reduced plasma Aβ42 and Aβ40 levels in younger and older adults and showed a trend toward increasing Aβ42/Aβ40 ratio only in older adults. The primary goal of the current study was to extend these findings in 62 adults aged 50 to 70 years using randomized assignment to 10 weeks of slow-paced breathing or a random-paced breathing control with three assessment time points. Secondary objectives included examining the effects of slow-paced breathing on brain structure (i.e., perivascular space and hippocampal volumes) and cognitive performance. Consistent with prior findings, the slow-paced breathing group showed greater decreases in plasma Aβ42 than the control group. However, group differences were not significant for Aβ40 or Aβ42/Aβ40 ratios, and no significant effects were observed for the secondary outcomes. The non-significant findings may be due to changes we made to both intervention and control condition methods relative to our previous trial. Further research is needed to explore the underlying mechanisms and potential effects of slow-paced breathing on Aβ accumulation in the brain.

HIGHLIGHTS: Participants were randomly assigned to slow-placed breathing or a breathing controlIndividualized protocols determined breathing pacesTen weeks of daily slow-paced breathing practice reduced plasma Aβ42 levels.},
}

@article {pmid41542671,
year = {2026},
author = {Ghanbarian, E and Khorsand, B and Zheng, L and Woodworth, DC and Glover, CM and Corrada, MM and Grill, JD and Sajjadi, SA and , and Ezzati, A},
title = {Hippocampal Asymmetry Captures Non-Amyloid-Related Risk of Memory Decline and Clinical Progression.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.06.26343553},
pmid = {41542671},
abstract = {BACKGROUND: Hippocampal atrophy is a key marker of Alzheimer's disease (AD)-related neurodegeneration; however, hippocampal volume alone may not fully capture heterogeneity in cognitive decline. Hemispheric hippocampal asymmetry may provide complementary information, but its prognostic value for cognitive decline and clinical progression remains unclear.

METHODS: We studied 1,142 dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available baseline structural MRI, cerebrospinal fluid (CSF) amyloid-β (Aβ42) and phosphorylated tau (p-tau-181), and longitudinal cognitive follow-up. Total hippocampal volume (left + right) and hemispheric asymmetry (absolute left-right volumetric difference) were modeled simultaneously. Linear mixed-effects models examined associations with baseline performance and longitudinal change across memory, language, executive, and visuospatial domains. Cox proportional hazards models assessed risk of clinical progression to clinical dementia over up to 10 years of follow-up. All analyses adjusted for age, sex, education, APOE ε4 status, and CSF biomarkers, with stratification by amyloid status.

RESULTS: The study cohort included 546 women (47.8%), with a mean age of 72.54 ± 6.98 years. Larger total hippocampal volume was consistently associated with better baseline performance and slower decline across all four cognitive domains, independent of amyloid and tau biomarkers. In contrast, greater hippocampal asymmetry was selectively associated with worse baseline memory performance and faster memory decline, independent of total hippocampal volume. In amyloid-stratified analyses, total hippocampal volume showed broad associations with cognition across all four domains among amyloid-positive participants and more limited, domain-specific associations among amyloid-negative participants, whereas hippocampal asymmetry was associated with memory only in amyloid-negative individuals. Regarding clinical progression to dementia, smaller total hippocampal volume was associated with higher risk of progression in the overall cohort and within both amyloid groups. In contrast, hippocampal asymmetry was associated with progression risk only among amyloid-negative individuals (hazard ratio per SD increase = 1.31, 95% CI: 1.03-1.65).

CONCLUSIONS: Hippocampal total volume and asymmetry capture distinct aspects of neurodegeneration, with asymmetry providing additional prognostic information for memory decline and clinical progression in participants without detectable amyloid pathology.},
}

@article {pmid41542587,
year = {2026},
author = {Feng, S and Coursey, SE and Nolin, SA and Zurcher, NR and Wey, HY and Polimeni, JR and Villien, M and Bhanot, A and Rosen, BR and Hooker, JM and Chen, JE},
title = {Energetic implications of fMRI-based nodal complex network metrics: a complex picture unfolds across diverse brain states.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.08.694967},
pmid = {41542587},
issn = {2692-8205},
abstract = {Functional MRI-based graph theory has provided profound insights into the brain's functional organization, yet the neuroenergetic meaning of widely used graph-theoretical metrics remains poorly understood. Although resting-state research suggests a positive coupling between network topology and glucose metabolism, it remains unclear whether this relationship reflects a general principle of brain organization or a state-specific phenomenon. Here, we test the neuroenergetic interpretability of nodal graph-theoretical metrics by linking complex network topology to cerebral glucose consumption across diverse brain states. Leveraging simultaneous functional PET-MRI, we directly compare state-dependent fluctuations in glucose consumption and network topology during sensory, cognitive, and arousal conditions. We further assess metabolic-topological couplings in disease through a meta-analysis of resting-state FDG-PET and fMRI studies involving Alzheimer's disease, Parkinson's disease, major depressive disorder, and schizophrenia. Our results show that nodal graph-theoretical metrics exhibit state- and network-dependent metabolic associations, with coupling patterns diverging across experimental and disease contexts. Notably, frontoparietal and attentional networks show more conserved metabolic-topological coupling than other large-scale networks across states. These findings underscore a dynamic, complex interplay between metabolic demand and complex network organization, highlighting the need for a nuanced interpretation of the energetic underpinnings of nodal graph-theoretical metrics in health and disease.},
}

@article {pmid41542504,
year = {2026},
author = {Shkirkova, K and Maria, NSS and Anson, H and Aghaei, Y and Badami, MM and Chakhoyan, A and Godoy-Lugo, JA and Chung, C and Durra, S and Tang-Tan, A and Zhao, L and Demetriou, A and Morales, M and Daggupati, S and Bent, I and Park, H and Franklin, C and Chen, S and Chahine, G and Dodds-Lewis, S and Morishita, M and Jacobs, RE and Gout, JF and Mack, WJ and Forman, HJ and Benayoun, BA and Vermulst, M and Cohen, MD and Campen, M and Sioutas, C and Mack, WJ and Finch, CE and Thorwald, MA},
title = {Induction of ferroptotic and amyloidogenic signatures linked to Alzheimer's disease by chemically distinct air pollutants.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.06.696601},
pmid = {41542504},
issn = {2692-8205},
abstract = {Air pollution (AirP) exposure is associated with increased Alzheimer's disease (AD) risk, yet AirP is chemically heterogeneous, complicating identification of shared pathogenic drivers. We examined acute cortical responses to two metal-rich AirP sources, diesel exhaust particles (DEP) and World Trade Center (WTC) dust, and compared them to woodsmoke (WS), a particulate exposure with low metal content. DEP and WTC elicited highly convergent transcriptional responses, sharing over 1200 differentially expressed genes linked to inflammation, ferroptosis, neuronal remodeling, and amyloid processing. These changes were accompanied by impaired antioxidant activity and increased lipid peroxidation within lipid rafts, a membrane microdomain critical for amyloid processing, resulting in increased Aβ generation. In contrast, WS produced a distinct transcriptional signature and failed to induce ferroptotic priming or lipid peroxidation, consistent with its low metal composition. Together, these findings implicate metals as a shared driver linking diverse AirP exposures to amyloidogenic vulnerability and elevated AD risk.},
}

@article {pmid41542451,
year = {2026},
author = {Pelletier, A and Tuck, T and Tcw, J},
title = {Factorization of Alzheimer's disease genetic risk influences allow patient stratification, predicting disease onset, cognitive decline, and cell-type specific responses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.02.697432},
pmid = {41542451},
issn = {2692-8205},
abstract = {Late-onset Alzheimer's disease (AD) is a complex and heterogeneous neurodegenerative disease with significant genetic components implicated in at least 97 loci from AD genome-wide association studies. While various distinct AD subtypes have been identified based on brain or CSF molecular profiling, contribution of the genetic signatures in distinguishing the AD subtypes is lacking. Here, we leveraged large snRNA-seq postmortem brain data with an empirical Bayes matrix factorization (EBMF) approach to study common effects of 197 AD risk variants on neuronal and glial cell transcriptome, enabling factor-based polygenic score (fPGS) and patient clustering based on their functional genetic profiles. We confirmed that each factor captures specific AD risk variant influences on cell types and known AD-associated biological processes, such as mitochondrial activity, endo-lysosomal activity, mRNA processing, neuroinflammation, or calcium signaling. Further, we found that most fPGS were predicting a certain neuropathological or AD-associated molecular condition. Notably, fPGS3 predicts somatic mutation burden in excitatory neurons, and fPGS7 predicts epigenome erosion in excitatory neurons associated with lipid transport disorders, increased mitochondrial activity, and increased Tau pathology. Finally, unsupervised clustering analysis of individuals with mild cognitive impairment and AD based on their fPGS profiles enable us to identify seven clusters, which are differentiated by the APOE genotype. Among them, five groups were subdivided within APOE3 homozygotes, which remarkably predicted either the disease severity or the disease onset with up to 6 years differences among groups. Resilient groups were associated with reduced matrisome and reactivity in astrocytes and increased cholesterol metabolic pathways in oligodendrocytes and OPCs. Overall, the analyses confirmed the ability of EBMF to stratify AD risk variant influences into molecularly and clinically coherent factors that allow genetic predictions of particular cell types and alterations of biological processes impacting the disease.},
}

@article {pmid41542441,
year = {2026},
author = {Kana, OZ and Postupna, N and Agrawal, A and Long, B and Travaglini, KJ and Gabitto, MI and Lai, HY and Mahoney, JT and Xiao, M and Bajwa, T and Hulsey-Vincent, H and Oyaizu, SL and Mena, GE and Hong, J and Gelfand, EC and Kaplan, ES and Ariza, J and Smith, KA and McMillen, DA and Chakka, AB and Goldy, J and Melief, EJ and Barta, S and Oyama, A and Ruiz, A and Pom, CA and Ayala, A and Bixby, M and Huang, A and Martin, N and Cuevas, NV and Olsen, P and Nagra, J and Chakrabarty, R and Tieu, M and Cardenas, T and Torkelson, A and Bertagnolli, D and Guzman, J and Ferrer, R and Waters, J and Grabowski, TJ and Crane, PK and Gatto, NM and Miller, JA and Hodge, RD and Hawrylycz, M and Keene, CD and Lein, ES and Close, JL},
title = {The Caudate Nucleus Exhibits Distinct Pathology and Cell Type-Specific Responses Across Alzheimer's Disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.10.694705},
pmid = {41542441},
issn = {2692-8205},
abstract = {Aβ presence in the caudate nucleus (Ca) partially defines Thal stage III in Alzheimer's disease (AD), but little is known about AD's cellular impact on the region. Leveraging a public basal ganglia taxonomy of cellular populations, we generated a cellular resolution atlas of AD-associated pathological changes in Ca. Unlike cortex, we found that Ca AD pathology is dominated by two key features: phosphorylated tau (pTau)-containing neuropil threads enriched near oligodendrocytes in white matter tracts and amyloid-β diffuse plaques enriched in gray matter. Although AD pathology in affected cortical regions results in neuronal loss, we find no AD-driven reductions in neuron proportions in Ca. However, there were observable changes in multiple cellular populations. Protoplasmic astrocytes and FLT1+/IL1B+ microglia increased in abundance with global pTau levels. We also observe gene expression changes in fast-spiking PTHLH-PVALB interneurons indicative of disrupted signaling pathways and altered intrinsic physiological properties. This work provides a cellular-resolution framework for understanding AD pathology in Ca.},
}

@article {pmid41542218,
year = {2026},
author = {Schickedanz, H and Safaeipour, C and Sherzai, D and Sherzai, A},
title = {Effects of Lifestyle Medicine on Alzheimer's Disease: Insights From Emerging Evidence and Multi-Domain Interventions.},
journal = {American journal of lifestyle medicine},
volume = {},
number = {},
pages = {15598276261417271},
pmid = {41542218},
issn = {1559-8284},
abstract = {Alzheimer's Disease (AD) and related dementias, encompassing primarily neurodegenerative but also mixed etiologies, represent a mounting public health concern expected to affect over 15 million Americans by 2060. This review synthesizes emerging evidence on how Lifestyle Medicine can meaningfully reduce risk and slow the progression of dementia. While genetic factors contribute to AD, mounting data highlight the central role that modifiable lifestyle factors, including nutrition, physical activity, sleep hygiene, stress management, social and cognitive engagement, and sensory health, play in its pathogenesis and trajectory. Mediterranean-type diets, regular exercise, robust sleep, stress mitigation, and social connectedness are associated with lower dementia risk, while smoking, excess alcohol, and chronic psychological stress elevate risk. Integrative strategies, such as mindfulness meditation and sensor-based digital monitoring, hold promise for individualized prevention and care. Culturally informed, holistic approaches addressing structural barriers and supporting caregivers are critical for equitable dementia prevention. This review presents compelling evidence that Lifestyle Medicine implemented in tandem with emerging technologies offers a scalable, cost-effective, and patient-centered framework for reducing the impact of AD and related dementias while enhancing well-being among patients, families, and communities.},
}

@article {pmid41542065,
year = {2026},
author = {Karim, F and Biju, AP and Liang, C and Santos, CJ and Rajarethenam, M and Mukherjee, J},
title = {Evaluation of [18F]MK-6240 binding to tau protein in postmortem human brains of Down syndrome and Alzheimer's disease and assessment of off-target (non-tau) binding.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8463304/v1},
pmid = {41542065},
issn = {2693-5015},
abstract = {Alzheimer's disease (AD) and Down Syndrome (DS) are characterized by the aggregation of tau tangles. As a novel tau PET tracer in AD, [ [18] F]MK-6240 has the potential in DSAD to elucidate pathophysiology and advance diagnostic strategies. Autoradiography of frontal cortex (FCX) and temporal cortex (TCX) postmortem brain slices of DSAD (n = 5), AD (n = 5), and cognitively normal (CN) (n = 5) cases indicated similarly high [ [18] F]MK-6240 binding in DSAD and AD cases. Anti-tau immunostains confirmed total tau presence so there was alignment in anti-tau abundance with quantification of [ [18] F]MK-6240 binding. DSAD and AD cases exhibited higher gray matter (GM)/white matter (WM) ratios of 2.8 and 2.5 respectively. For drug effects on [ [18] F]MK-6240 binding, self-displacement of [ [18] F]MK-6240 was by 88% among DSAD cases and 85% among AD cases while IPPI displaced [ [18] F]MK-6240 by 81% and 74% in DSAD and AD cases respectively. KuFal194, a specific phosphokinase inhibitor, minimally displaced [ [18] F]MK-6240 binding. Harmine competed with [ [18] F]MK-6240 with an IC 50 value of 290 ± 218 nM and 92 ± 15 nM for DSAD and AD cases, respectively, suggesting unique tau binding. High meninges off-target (non-tau) binding of [ [18] F]MK-6240 was observed in a CN case, comparable to the GM in DSAD and AD. MK-6240 (10 µM) blocked 44% and T807 (10 µM) blocked 30% of meninges binding. Incubation of meninges in the presence of 0.2% polyethylenimine reduced 70% of [ [18] F]MK-6240 binding. The tau imaging agent, [ [125] I]IPPI, an analog of [ [18] F]MK-6240, exhibited minimal binding to CN meninges. Our findings suggest [ [18] F]MK-6240 to be selective tau imaging agent in DSAD and AD, harmine to be a weak tau drug, and off-target nonspecific meninges binding maybe due to the primary aromatic amine group in [ [18] F]MK-6240.},
}

@article {pmid41542061,
year = {2026},
author = {Lukacsovich, D and Young, J and Gomez, L and Kunkle, B and Mao, Z and Zhang, W and Chen, XS and O'Shea, D and Rundek, T and Martin, E and Wang, L},
title = {DNA methylation signature of cognitive reserve moderates CSF tau pathology in prodromal Alzheimer's disease.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8369919/v1},
pmid = {41542061},
issn = {2693-5015},
abstract = {Background Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no established blood-based biomarkers of CR in prodromal AD. In this study, we operationalize CR as memory reserve, defined as moderation (attenuation) of the CSF pTau181-memory association. DNA methylation (DNAm) integrates genetic and environmental influences and may capture biological processes that mitigate the impact of AD pathology on memory. We aimed to identify blood DNAm loci that moderate the association between cerebrospinal fluid (CSF) phosphorylated tau (pTau181) and memory in mild cognitive impairment (MCI). We also sought to determine if a DNAm-based signature of memory reserve predicts future memory decline. Methods We analyzed 92 amyloid positive MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with blood DNAm, CSF pTau181, and memory scores (PHC_MEM) collected at the same visit. We first regressed memory scores on covariates (age, sex, number of APOE4 alleles, estimated major immune cell type proportions) and used the residuals as covariate-adjusted memory scores. At each CpG, we then fitted linear models of memory on DNAm, pTau181, and their interaction. Inflations were corrected using the bacon method. We identified differentially methylated regions (DMRs), assessed pathway enrichment, and performed integrative analyses incorporating external resources including expression quantitative trait methylation (eQTM), methylation quantitative trait loci (mQTL) databases, AD genome-wide association study summary statistics, and blood-brain DNAm correlations. A methylation score was constructed and evaluated in linear mixed-effects models of longitudinal memory in 88 participants with follow-up information. Results After removing CpGs with low variability, we identified 6 CpGs with suggestive significance for DNAm×pTau181 interaction (P- value < 1×10 [-5]) and 11 DMRs that passed multiple comparisons correction. These loci mapped to genes involved in synaptic function, vascular and blood-brain barrier integrity, amyloid clearance, immune and metabolic regulation. Almost all showed no strong marginal associations with pTau181 or memory, supporting a moderating rather than mediating role. Pathway analysis revealed enrichment of adipocytokine signaling and adipose metabolic pathways, and a number of CpGs associated with mQTLs overlapped with AD genetic risk loci. A higher baseline MRS attenuated the pTau-memory association and significantly associated with slower future memory decline, independent of age, sex, education, APOE ε4, and baseline pTau181. Conclusions Blood DNAm patterns that moderate the pTau-memory relationship capture biology underlying memory reserve involving synaptic, vascular, immune, and metabolic pathways, and can be summarized into an MRS that predicts longitudinal memory trajectories in MCI. These findings support blood DNAm as a promising, non-invasive biomarker of cognitive resilience to AD pathology.},
}

@article {pmid41541891,
year = {2025},
author = {Jia, A and Zhou, Y and Xu, X and Gao, X and Liu, Y and Li, X and Bai, Y and Yu, X and Zhou, M},
title = {The Evolution of Patterns of Mortality and Disability Burden Among Older Adults - China, 1990-2023.},
journal = {China CDC weekly},
volume = {7},
number = {52},
pages = {1609-1614},
pmid = {41541891},
issn = {2096-7071},
abstract = {China's aging population has a heavy chronic disease burden. Existing research often overlooks health heterogeneity among older age groups, relies on mortality metrics, and lacks information on long-term disability trends.

WHAT IS ADDED BY THIS REPORT?: This study reveals that all-cause mortality declined substantially, whereas years lived with disability (YLDs) remained stable. Alzheimer's disease and other dementias (ADOD) exhibited the fastest increase in mortality [average annual percent change (AAPC)=1.76, 95% confidence interval (CI): 1.63, 1.87]. Age-related hearing loss and falls dominated YLDs.

Public health strategies should shift from general approaches to age-tailored interventions. Integrating evidence-based stratified strategies is crucial for reducing disability and advancing Healthy China by 2030.},
}

@article {pmid41541749,
year = {2026},
author = {Cano Urrego, B and Alsup, A and Thompson, JA and Koestler, DC},
title = {A stochastic approach to k-nearest neighbors search using a fixed radius method.},
journal = {Computational statistics},
volume = {41},
number = {1},
pages = {27},
pmid = {41541749},
issn = {0943-4062},
abstract = {This study aims to optimize the [Formula: see text]-nearest neighbors search (kNN search) by reducing the computational burden of the well-known Brute-force method while providing the same solution. While there exist rule-based approaches for reducing the computational burden of the kNN search, methods that use the stochastic patterns inherent to the data are lacking. Our method leverages data structures and probabilistic assumptions to enhance the scalability of the search. By focusing on the Training set where our neighbors reside, we define a sample space that limits the [Formula: see text]-nearest neighbors search to a smaller space. For each observation in the Query set (e.g., the set of observations for which a classification is desired), a fixed radius search is employed, with the radius stochastically linked to the desired number of neighbors. This approach allows us to find the [Formula: see text]-nearest neighbors using only a fraction of the entire Training set in contrast to the Brute-force method, which requires distances to be calculated between each observation in the Training set and each observation in the Query set. Through simulations and a theoretical computational complexity analysis, we demonstrate that our method outperforms the Brute-force approach, particularly when the Training and Query set sample sizes are large. In addition, a benchmarked comparison of our approach and the Brute-force method on an Alzheimer's disease data set further demonstrated this, showing a 27.57-fold improvement in total elapsed time. Overall, our stochastic approach significantly reduces the computational load of kNN search while maintaining accuracy, making it a viable alternative to traditional methods for large datasets.},
}

@article {pmid41541747,
year = {2025},
author = {Theisz, AA and Bosco, C and Torres, JO and Shojaei, F and Lin, J and Cureton, B and Himes, AK and Jessup, NM and Barnes, PA and Lu, Y and Hendrie, HC and Hill, CV and Shih, PC},
title = {Exploring Design Recommendations for Promoting Brain Health, ADRD Health Literacy, and Participation in clinical ADRD trials in Older African American/Black Adults.},
journal = {Proceedings of the ACM on human-computer interaction},
volume = {9},
number = {2},
pages = {},
pmid = {41541747},
issn = {2573-0142},
support = {R24 AG071471/AG/NIA NIH HHS/United States ; },
abstract = {Alzheimer's Disease and related dementia (ADRD) is prevalent in one in nine individuals age 65 or above, and it has a 65% higher risk of incidence for African American/Black adults. With an aging population in the United States and persisting healthcare inequities for African American/Black adults, our research aims to explore design requirements of a digital health platform for delivering culturally relevant content that informs African Americans/Black adults (45 years and older) about brain health and participation in clinical ADRD studies. We conducted seven focus groups (n = 44) to collect information on facilitators and barriers to brain health literacy and participation in clinical ADRD research, followed by seven participatory design workshops (n = 44) to collaboratively develop solutions for improving brain health literacy and participation in clinical ADRD research. Our findings provide insights into incorporating community into accessible, technological design for reducing brain health disparities for African American/Black adults.},
}

@article {pmid41541199,
year = {2026},
author = {Salah, RS and El-Sayed, NF and El-Hussieny, M and Mansour, ST and Othman, M and Fouad, MA and Rashdan, HRM and Ewies, EF and Gharib, HSA and Elsayed, GH},
title = {Design and synthesis of new phosphazine and triazole derivatives for treatment of Alzheimer's disease: modulating ROS/JNK and Wnt/β-catenin signaling pathways.},
journal = {RSC advances},
volume = {16},
number = {4},
pages = {3077-3100},
pmid = {41541199},
issn = {2046-2069},
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive impairment and the accumulation of amyloid-β (Aβ) peptides. In this study, a novel series of triazole and phosphazine derivatives were synthesized and evaluated for neuroprotective activity in an aluminum chloride (AlCl3)-induced rat model of AD. Among the synthesized compounds, 3a, 6a, and 6c were structurally characterized and selected for in vivo biological evaluation. Behavioral, biochemical, molecular, and histopathological assessments were conducted to determine their efficacy, with Rivastigmine used as a reference drug. Compounds 3a and 6c significantly improved cognitive and memory performance, decreased Aβ1-42 production, and reduced reactive oxygen species (ROS) generation. Furthermore, both compounds inhibited the activation of JNK and Puma, promoted Beclin-1 expression, and activated Wnt/β-catenin signaling, as evidenced by increased expression levels of Wnt7a, β-catenin, LRP6, and FZD4, alongside decreased expression levels of GSK-3β and BACE1. Molecular docking studies supported these findings, revealing strong binding affinities of the active compounds, particularly 3a, to the JNK3 active site. Molecular dynamic simulations were performed on the best docking pose of the most potent compound 3a to confirm the formation of a stable complex with JNK3. Compounds 3a, 6a, and 6c demonstrated favorable pharmacokinetic profiles, with predicted good oral bioavailability, blood-brain barrier permeability, and non-substrate behavior toward P-glycoprotein. They are expected to maintain therapeutic availability in systemic circulation, as indicated by the predicted plasma protein binding below 90%, moderate to high steady-state volume of distribution, and lack of substrate affinity for cytochrome P450 enzymes CYP2C9 and CYP2D6. These results suggest that compounds 3a and 6c may serve as promising multi-target therapeutic candidates for AD by modulating oxidative stress, apoptosis, autophagy, and Wnt/β-catenin signaling pathways.},
}

@article {pmid41541005,
year = {2026},
author = {Wiebe, E and Olayiwola, Z and Adebiyi, O},
title = {Tracing the threads: How toxic metals contribute to neurodegeneration.},
journal = {IBRO neuroscience reports},
volume = {20},
number = {},
pages = {34-48},
pmid = {41541005},
issn = {2667-2421},
abstract = {Brain disorders affect more than one in three people globally, representing a leading cause of disability and morbidity. While the etiology of several of these disorders remains elusive, it is increasingly evident that both genetic and environmental factors contribute to their onset and progression. Given the persistent effects of environmental exposures on biological systems, this review highlights the role of heavy metals (particularly lead, mercury, vanadium, and chromium) in altering behaviour and contributing to the development of neurodegenerative and demyelinating diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We discuss the sources of human and animal exposure to these metals, focusing on the underlying mechanisms by which they promote neurotoxicity, including oxidative stress, mitochondrial dysfunction, protein aggregation, and disruption of the blood-brain barrier. Additionally, we explore how exposure affects genetic and epigenetic interactions and provide epidemiological data linking metal toxicity to brain disorders. By exploring evidence from animal models and human epidemiological studies, with public health relevance, we extend our discussion beyond descriptive neurotoxicology to highlight exposure to these metals as a unifying upstream driver of various brain disorders. Finally, considering gaps in current knowledge, particularly regarding the impact of transgenerational exposures, we propose directions for future research. These insights not only enhance our understanding of metal-induced neurodegeneration but also underscore the need for targeted public health interventions and policies to reduce exposure, especially in vulnerable populations and communities.},
}

@article {pmid41540959,
year = {2026},
author = {Ajith, A and Tripathi, SM and Jayasree, P and Surendran, HK and Chowdhury, M and Ghanti, A and Narayana, C and Bhowmik, D},
title = {Selective detection of membrane-bound amyloid-β oligomers using SERS "hot-spots": toward early diagnostics for Alzheimer's disease.},
journal = {Nanoscale},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5nr03999a},
pmid = {41540959},
issn = {2040-3372},
abstract = {A key characteristic of Alzheimer's disease (AD) is the build-up of amyloid-β (Aβ) fibrillar aggregates, commonly known as plaques, within the brain. Current diagnostic tools, such as MRI, CT, and PET, primarily detect neurodegeneration or plaque burden, limiting their utility to advanced stages of the disorder. Thus, there is a strong need for sensitive approaches that can enable detection at the earliest. Aβ aggregation begins with the formation of small, lipophilic oligomers characterized by antiparallel β-sheet structures. Emerging evidence suggests that these oligomers associated with exosomes can traverse the blood-brain barrier, with their peripheral blood levels reflecting disease progression. However, their low abundance poses a significant detection challenge. Sensitive and selective detection of these lipophilic oligomers could provide a powerful diagnostic tool for early AD detection. In this work, we introduce a highly sensitive Surface-Enhanced Raman Spectroscopy (SERS)-based platform for detecting membrane-bound Aβ oligomers. Monodisperse silver nanoparticles (AgNPs) were functionalized with Rose Bengal (RB), a dye specific to amyloid oligomers. Separately, lipid-bilayer-coated AgNPs were used to capture lipophilic Aβ oligomers. The interaction between the oligomers and RB localized the dye molecules within SERS "hot spots" formed between the nanoparticles, leading to a robust, Aβ-concentration-dependent enhancement of the RB Raman signal. This dual-nanoconstruct system provides a promising route toward blood-based early-stage AD diagnostics.},
}

@article {pmid41540764,
year = {2026},
author = {Kanwal, A and Azeem, B and Nasir, H and Mumtaz, F and Ashraf, N and Amin, MHJ and Kanwal, W and Khan, BW},
title = {Exploring Adjunctive Novel Therapeutic Approach of KarXT (Xanomeline-Trospium Chloride) for Managing Psychotic Symptoms in Patients With Schizophrenia and Alzheimer's Disease.},
journal = {Brain and behavior},
volume = {16},
number = {1},
pages = {e71182},
pmid = {41540764},
issn = {2162-3279},
mesh = {Humans ; *Alzheimer Disease/drug therapy/complications ; *Schizophrenia/drug therapy/complications ; *Psychotic Disorders/drug therapy ; *Antipsychotic Agents/pharmacology/therapeutic use ; Quality of Life ; },
abstract = {BACKGROUND: Acute psychotic symptoms like delusions and hallucinations are of major concern while treating patients with schizophrenia and alzheimer's psychosis, primarily impacting their daily life functioning and quality of life. The traditional antipsychotic medications, commonly prescribed to manage these symptoms, cause significant side effects with limited efficacy, requiring novel therapeutic agents that can overcome this challenge. While there is no definitive cure, symptomatic treatment can help relieve some of the symptoms and improve the quality of life of people with alzheimer's disease (AD).

METHOD: A comprehensive literature search of PubMed, scopus, google scholar, and ClinicalTrials.gov was conducted to identify studies on xanomeline-trospium chloride (KarXT) in schizophrenia and AD psychosis. After screening 802 unique records, 39 studies-including preclinical, clinical, and observational investigations-were included in this narrative review. Only English-language publications up to February 2025 were considered.

RESULT: KarXT, with its dual action on the M1 and M4 receptors and mAChR antagonism, greatly helps reduce the severity of the positive and negative symptoms, as it resulted in an 8.4-point greater reduction on the PANSS scale. Side effects were minimal and did not account for the discontinuation of treatment.

CONCLUSION: Psychosis is a common feature of schizophrenia and AD, most often caused by high concentrations of dopamine in the brain, characterized by hallucinations, delusions, and disorganized thinking, resulting in markedly reduced quality of life for the patient and associated caregiver. Conventional treatments targeting dopamine receptors produce extrapyramidal symptoms and metabolic side effects, leading to noncompliance with medication. KarXT, with its dual action on M1 and M4 receptors and mAChR antagonism, greatly helps reduce the severity of the positive and negative symptoms. The side effects experienced were minimal and did not account for the discontinuation of treatment.An overview of the mechanism of action, clinical trials, and classical findings of KarXT for the management of psychotic symptoms in patients with schizophrenia and alzheimer's disease.},
}

Humans
*Alzheimer Disease/drug therapy/complications
*Schizophrenia/drug therapy/complications
*Psychotic Disorders/drug therapy
*Antipsychotic Agents/pharmacology/therapeutic use
Quality of Life

@article {pmid41540706,
year = {2026},
author = {Zhang, S and Huang, T and Yang, C and Chen, J and Lü, T and Zhang, J},
title = {[Sulforaphane reduces reactive astrocyte-mediated neuron apoptosis in vitro by inhibiting the MAPK/NF-κB signaling pathway in Aβ42 oligomer-activated astrocytes].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {46},
number = {1},
pages = {191-199},
pmid = {41540706},
issn = {1673-4254},
mesh = {*Isothiocyanates/pharmacology ; *Astrocytes/cytology/drug effects/metabolism ; Sulfoxides ; *Apoptosis/drug effects ; *Amyloid beta-Peptides/pharmacology ; *Neurons/cytology/drug effects/metabolism ; Signal Transduction/drug effects ; Humans ; Animals ; NF-kappa B/metabolism ; Mice ; Coculture Techniques ; Peptide Fragments/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Cell Line, Tumor ; Interleukin-6/metabolism ; },
abstract = {OBJECTIVES: To explore the effects of sulforaphane (SFN) on Aβ42-activated U87 astrocyte-mediated apoptosis of SH-SY5Y neurons in vitro.

METHODS: U87 cells treated with different concentrations of Aβ42, SFN or both were examined for changes in cell activity, IL-6 and TNF-α mRNA expression, release of IL-6 and TNF-α proteins, and expressions of p-p38, p-p65 and GFAP using CCK-8 assay, RT-qPCR, ELISA and Western blotting. SH-SY5Y neurons were co-cultured with U87 astrocytes treated with Aβ42 alone or in combination with SFN or SB203580 for 24 h, and the changes in Bax protein expression levels and viability of SH-SY5Y cells were examined. The effects of Aβ42, SFN, and their combination were also observed in astrocytes isolated from mouse brain tissues, and the indirect effects of astrocyte treatmentt on viability of the co-cultured primary neurons were assessed.

RESULTS: The viability of U87 astrocytes increased significantly following treatment with 1.25 μmol/L Aβ42 but decreased after Aβ42 treatment above 5 μmol/L. SFN treatments for 24 h below 5 μmol/L did not significantly affect U87 cell viability. Aβ42 treatment significantly increased protein expressions of p-p38, p-p65 and GFAP, mRNA expression levels of IL-6 and TNF-α, and IL-6 and TNF-α levels in culture supernatant of U87 cells. SH-SY5Y cells co-cultured with Aβ42-treated U87 cells showed significantly increased protein expressions of Bax, and exhibited lowered viability following co-culture with 5 μmol/L Aβ42-treated U87 cells. The isolated mouse astrocytes showed lowered viability following Aβ42 treatment above 10 μmol/L, but SFN treatment below 5 μmol/L for 24 did not obviously affect the cell viability. The primary neurons co-cultured with Aβ42-treated mouse astrocytes showed significantly lower cell viability than those co-cultured with the astrocytes treated with Aβ+SFN or Aβ+SB203580.

CONCLUSIONS: SFN attenuates astrocyte-mediated neuron apoptosis by inhibiting the MAPK/NF-κB signaling pathway in Aβ42 oligomer-activated astrocytes.},
}

*Isothiocyanates/pharmacology
*Astrocytes/cytology/drug effects/metabolism
Sulfoxides
*Apoptosis/drug effects
*Amyloid beta-Peptides/pharmacology
*Neurons/cytology/drug effects/metabolism
Signal Transduction/drug effects
Humans
Animals
NF-kappa B/metabolism
Mice
Coculture Techniques
Peptide Fragments/pharmacology
Tumor Necrosis Factor-alpha/metabolism
Cell Line, Tumor
Interleukin-6/metabolism

@article {pmid41540543,
year = {2026},
author = {Singh, NK and Kumar, Y and Chandra, M and PadmaPriya, G and Sharma, Y and Mishra, S},
title = {Betanin: A Natural Phytomolecule for the Intervention of Neurological Disorders.},
journal = {Current topics in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680266398457251014040532},
pmid = {41540543},
issn = {1873-4294},
abstract = {Betanin is widely consumed around the globe either as beetroot directly or as one of the key ingredients in food and pharmaceutical preparations. The health benefits of Betanin, including the treatment of numerous neurological diseases and brain cancer, have been reported extensively. Betanin has gained global attention due to notable anti-inflammatory, antioxidant, and anti-cancer activities. Recently, there has been growing attention on the usage of Betanin to prevent or delay the onset of neurodegenerative disorders. This review recapitulates available information from various recent pre-clinical studies on Betanin in several neurological diseases, such as Parkinson's disease, Alzheimer's disease, aging, brain stroke, anxiety, and neuropathic pain. Betanin exhibits remarkable neuroprotective effects via activation of the Nrf2 signaling pathway, inhibition of the production and expression of pro-inflammatory mediators and reactive oxygen species, along with suppression of the NF-κB signaling pathway. Taking betanin as part of a healthy diet may aid in the management of various brain-related disorders. This review focuses on the neurological conditions for which betanin has shown therapeutic potential, highlighting its beneficial properties, cellular and molecular mechanisms of action, and its relevance in light of current research. Based on the available evidence, betanin could be considered a promising candidate and lead compound in the drug development process for the prevention, treatment, and management of several neurological disorders in the future.},
}

@article {pmid41540541,
year = {2026},
author = {Puri, BK and Lee, GS and Preyer, R and Schwarzbach, A},
title = {Hippocampal Function and Markers of Citrullinated Proteins and Bacterial and Viral Infection in Fibromyalgia.},
journal = {Current rheumatology reviews},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115733971382873251015113608},
pmid = {41540541},
issn = {1875-6360},
abstract = {INTRODUCTION: Fibromyalgia is associated with dyscognition or "fibro fog", of unknown aetiology. The hippocampus has major roles in memory and cognition. Certain bacterial and viral infections can cause hippocampal changes. Furthermore, citrullinated proteins may accumulate in the hippocampus in Alzheimer's disease.

OBJECTIVES: This study aimed to test the hypothesis that hippocampal functioning in fibromyalgia is associated with markers of bacterial and viral infection and serum anti-cyclic citrullinated pep-tide antibody (anti-CCP) levels.

METHODS: Hippocampal functioning was assessed in 26 female patients and one male patient with the Paired Associates Learning Total Errors (Adjusted) (PALTEA) in a cross-sectional study. Se-rum samples, for markers of bacterial and viral infections and anti-CCP, were taken within an hour of cognitive assessment.

RESULTS: Generalised linear modelling (p = 0.01) with PALTEA as the dependent variable showed significant coefficients for Borrelia outer surface protein peptide mix (p = 0.025), lymphocyte function-associated antigen-1 (p = 0.003), Ehrlichia chaffeensis plus Anaplasma phagocytophi-lum (p = 0.048), Mycoplasma pneumoniae immunoglobulin (Ig) G (p = 0.003), coxsackievirus B1 IgA (p = 0.010), echovirus IgG (p = 0.012), and anti-CCP IgG (p = 0.003).

CONCLUSION: On the basis of this study, it is suggested that, in fibromyalgia patients complaining of dyscognition, there may be merit in assessing lymphocyte function-associated antigen-1, anti-CCP IgG, and evidence of infection with Borrelia species, Ehrlichia chaffeensis, Anaplasma phagocytophilum, Mycoplasma pneumoniae, coxsackievirus B1, and echovirus.},
}

@article {pmid41540505,
year = {2026},
author = {Sundermann, EE and Banks, SJ and Bondi, MW and Martinez, MA and Biegon, A and Rotblatt, LJ and Hildebrandt, T},
title = {Sex differences in the relationship of biomarker change to memory decline in early Alzheimer's disease: an observational cohort study.},
journal = {Biology of sex differences},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13293-025-00820-6},
pmid = {41540505},
issn = {2042-6410},
support = {1R01AG074221/AG/NIA NIH HHS/United States ; 1R01AG074221/AG/NIA NIH HHS/United States ; 1R01AG074221/AG/NIA NIH HHS/United States ; 1R01AG074221/AG/NIA NIH HHS/United States ; 1R01AG074221/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) exhibits sex differences in pathology and cognitive trajectories. Understanding how these differences manifest across the Alzheimer's continuum can improve early detection, diagnostics, and interventions. We examined sex differences in the association between cerebrospinal fluid (CSF) pTau181/Aβ42 ratio changes and verbal memory decline across the preclinical and mild cognitive impairment (MCI) stages of AD.

METHODS: In this retrospective, longitudinal, observational study, data were extracted from 401 participants (age range: 55-87.8, 98% non-Hispanic White) of the Alzheimer's Disease Neuroimaging Initiative cohort study who were classified as either preclinical AD (78 females, 73 males) or MCI (104 females, 146 males) at baseline and had CSF pTau181/Aβ42 ratio and cognitive assessment data at at-least two timepoints. Using regression models, we examined the relationship between changes in CSF pTau181/Aβ42 and verbal memory across all available time points and the moderating role of sex and AD stage over a mean follow-up period of 4 years. Verbal memory was represented by a composite z-score averaging Learning and Delayed Recall z-scores of the Rey Auditory Verbal Learning Test. Covariates included baseline age, education, and apolipoprotein E genotype.

RESULTS: A significant sex * diagnostic group * biomarker change interaction (b=-17.47, 95%CI = 27.60 to -7.33, p = .001) indicated that sex differences in the relationship between changes in CSF pTau181/Aβ42 ratio and verbal memory differed by disease stage. While males in the preclinical AD stage showed steeper memory decline than females with increasing pTau181/Aβ42 ratios, this difference was not statistically significant. In contrast, in the MCI stage, a significant sex * biomarker change interaction (b = 10.17, 95% CI = 4.94 to 15.40, p < .001) indicated that females exhibited significantly steeper memory decline associated with increasing pTau181/Aβ42 ratios compared to males.

CONCLUSION: Sex differences in the relationship between AD biomarker levels and cognitive decline vary by disease stage. Although not statistically significant, females demonstrated resilience to memory decline in the preclinical stage, whereas, in the MCI stage, they experienced significantly steeper memory loss compared to males. Results suggest that accounting for sex in biomarker-based methods of disease detection and tracking can improve early detection and intervention in both sexes.},
}

@article {pmid41540503,
year = {2026},
author = {Song, C and Wu, PY and Huffman, WJ and David-Bercholz, J and Bedolla, A and Velagapudi, R and Njoroge, A and Rodriguiz, RM and Wetsel, WC and Rendina, D and Bilbo, SD and Chiang, W and Ogu, JC and Gelbard, HA and Yang, T and Grill, WM and Terrando, N},
title = {Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia.},
journal = {Bioelectronic medicine},
volume = {12},
number = {1},
pages = {2},
pmid = {41540503},
issn = {2332-8886},
support = {AARF-24-1313412/ALZ/Alzheimer's Association/United States ; 2019-AARG-643070/ALZ/Alzheimer's Association/United States ; R01-AG057525, R01-AG083979A1, RF1-AG079138, R21-AG055877/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Delirium and delirium superimposed on dementia (DSD) are common complications affecting patients suffering from ongoing neurodegenerative pathologies. Peripheral surgical trauma can trigger neuroinflammation and ensuing DSD via mechanisms that remain poorly understood. Given the multifactorial therapeutic effects of neuromodulation, including vagal nerve stimulation, we have tested a minimally invasive approach to combat DSD following orthopedic surgery.

METHODS: We performed orthopedic surgery on 5xFAD and CVN-AD mice and tested the efficacy of minimally invasive percutaneous vagus nerve stimulation (pVNS). We applied immunohistochemical, biochemical, and behavioral assays to evaluate the impact of surgery on postoperative delirium on DSD pathology in Alzheimer’s disease-like mice. To confirm the role of systemic factors in neuroinflammation and amyloid-β dyshomeostasis, we conducted experiments using interleukin-6 (IL-6), a cytokine commonly upregulated in postoperative delirium and in vitro co-culture assays for validation.

RESULTS: In AD-like mice surgery induced acute changes in amyloid-β; perioperative treatment with pVNS effectively reduced amyloid-β load, plaque sphericity, and neuronal loss. The rescue of these pathological hallmarks led to improved delirium-like behavior, as demonstrated by the 5-choice serial reaction time task on postoperative days 1 and 2. pVNS improved microglial morphology, particularly near amyloid-β plaques. Acute isolation of microglial cells from 5xFAD mice after surgery indicated that pVNS partially enhanced key Disease-Associated Microglia (DAM) markers. The contribution of pro-inflammatory cytokines to amyloid-β aggregation was validated using an in vitro transwell culture model following Cytomix exposure, which also caused endothelial barrier disruption. Finally, we isolated IL-6 as a well-established biomarker of postoperative delirium and described its role in DSD pathology following systemic administration.

CONCLUSION: These findings establish a role for neuromodulation after pVNS in regulating perioperative immunity and advance a new paradigm for perioperative interventions in patients at risk for DSD.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42234-025-00194-5.},
}

@article {pmid41540481,
year = {2026},
author = {Si, X and Tian, S and Chen, Y and Li, X and Wu, G and Yao, Y and Wang, M},
title = {Investigating the molecular mechanisms of glutamine metabolism and mitochondria-related biomarkers in Alzheimer's disease through transcriptomics and experimental validation.},
journal = {European journal of medical research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40001-025-03747-1},
pmid = {41540481},
issn = {2047-783X},
support = {22JR5RA994//Natural Science Foundation of Gansu Province, China/ ; CY2022-MS-A07//Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital, China/ ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. This study aims to identify biomarkers associated with glutamine metabolism-related genes (GRGs) and mitochondria-related genes (MRGs) in AD through bioinformatics analysis, offering insights for prevention and treatment strategies.

METHODS: Candidate genes were first picked out through differential gene expression profiling, construction of weighted gene co-expression network analysis (WGCNA), and interaction network analysis. Biomarkers were then filtered using machine learning algorithms. For these biomarkers, expression verification and receiver operating characteristic (ROC) curve analysis were carried out. These biomarkers underwent GeneMANIA analysis, subcellular and chromosomal localization, enrichment analysis, along with immune infiltration assessment, establishment of a multi-layered molecular regulatory network, and prediction of potential therapeutic agents by leveraging drug-gene interaction databases. Finally, the consistency was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).

RESULTS: Initially, 10 candidate genes were identified through bioinformatics analysis. Machine learning, expression validation, and ROC analysis pinpointed SNCA and PPP2R1A as biomarkers (AUC > 0.7). These biomarkers were associated with 20 functionally similar genes and were active in the nucleus and cytoplasm. SNCA was located on chromosome 4, and PPP2R1A on chromosome 19. Enrichment analysis unveiled their involvement in pathways such as olfactory transduction. Additionally, these biomarkers influenced immune cells; for instance, there was a positive correlation between PPP2R1A and type 2 T helper cells (cor = 0.66, P = 1.03 × 10[-5]). A molecular regulatory network demonstrated that these biomarkers were regulated by 134 miRNAs, and 72 potential drugs targeting these biomarkers were identified. RT-qPCR confirmed the expression consistency with bioinformatics results.

CONCLUSION: This study ultimately identified SNCA and PPP2R1A as biomarkers for AD, providing a theoretical foundation and potential targets for the diagnosis and treatment of AD.},
}

@article {pmid41540479,
year = {2026},
author = {Mee-Inta, O and Chiang, YY and Tsai, SF and Yang, TM and Zhao, ZW and Wang, TF and Wu, HY and Hsiung, CW and Liao, PC and Lee, HT and Huang, CC and Wu, PC and Kuo, YM},
title = {Running exercise mitigates amyloidosis in 5xFAD mice by improving the structure and function of the meningeal lymphatic system.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02218-2},
pmid = {41540479},
issn = {2051-5960},
}

@article {pmid41540476,
year = {2026},
author = {Zhang, Y and Zhang, F and Yin, H and Sun, Y and Wang, Y and Ren, Z and Jiang, J and Zeng, L},
title = {hUC-MSC-derived exosomes ameliorate Alzheimer's disease pathology through lncRNA-9969-mediated multi-target protection involving neuronal autophagy and microglial modulation.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-01954-4},
pmid = {41540476},
issn = {1758-9193},
support = {YDZJ202301ZYTS536//the Science and Technology Department of Jilin Province/ ; },
abstract = {BACKGROUND: Alzheimer's disease is characterized by intertwined pathologies including neuroinflammation, driven by microglial dysfunction, and metabolic disturbances such as lipid dyshomeostasis. Mesenchymal stem cell-derived exosomes (MSC-Exos) hold therapeutic promise, Still, it is unknown whether they can simultaneously address these co-occurring impairments via specific molecular cargos, such as long non-coding RNAs (lncRNAs).

METHODS: Transcriptome sequencing of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) revealed high expression of the long noncoding RNA ENST00000629969 (hereinafter referred to as lncRNA-9969). We isolated exosomes from hUC-MSCs (WT-Exo) and established human umbilical cord blood mesenchymal stem cells stably knocked down for lncRNA-9969 via siRNA, from which corresponding exosomes (KD-Exo) were isolated. Cross-species analysis identified the mouse homolog of lncRNA-9969 as ENSMUST00000200021 (hereinafter referred to as lncRNA-0021). Cellular experiments employed an Aβ₂₅₋₃₅-induced SH-SY5Y cell model to evaluate the protective effects of exosomes. In animal experiments, 6-month-old APP/PS1 mice received biweekly tail vein injections of WT-Exo or KD-Exo for 4 weeks. Phenotypic and mechanistic analyses were subsequently conducted using the Morris water maze, Western blot, immunofluorescence, qPCR, and transmission electron microscopy.

RESULTS: In Aβ-injured SH-SY5Y cells, WT-Exo significantly attenuated cellular damage and promoted Aβ clearance, whereas the protective effect of KD-Exo was markedly reduced. In APP/PS1 mice, WT-Exo treatment significantly improved spatial memory deficits and upregulated hippocampal expression of synaptic proteins synaptophysin (Syn) and brain-derived neurotrophic factor (BDNF). Molecular mechanism studies demonstrated that lncRNA-0021 directly binds mmu-miR-6361. Through this ceRNA mechanism, exosome-delivered lncRNA activated the mTOR/p70S6K autophagy pathway, regulated lipid metabolism-related genes, promoted microglial polarization toward the protective M2 phenotype, and suppressed pyroptosis. These beneficial changes were not observed in the KD-Exo-treated group.

CONCLUSIONS: hUC-MSC-derived exosomes exert neuroprotective effects by delivering functional lncRNA-9969. Its highly conserved homolog in mice, lncRNA-0021, achieves coordinated multi-target regulation of neuroinflammation, pyroptosis, and metabolic disturbances by sequestering miR-6361 and activating downstream signaling pathways. This study elucidates the central role of exosomal lncRNAs in AD pathology and provides new insights for developing RNA-based multi-target therapeutic strategies.},
}

@article {pmid41540459,
year = {2026},
author = {Shukla, S and Kadam, AA and Goyani, S and Jaiswal, N and Samantaray, K and Raghav, D and Kashyap, S and Tomar, D and Jadiya, P},
title = {Correction: Cell-type-specific dysregulation of mitochondrial calcium signalingin Alzheimer's disease.},
journal = {Cell communication and signaling : CCS},
volume = {24},
number = {1},
pages = {28},
pmid = {41540459},
issn = {1478-811X},
}

@article {pmid41540303,
year = {2026},
author = {Abd El-Fattah, MA},
title = {Challenges and Opportunities of Drug Delivery for Treatment of Alzheimer's Disease.},
journal = {AAPS PharmSciTech},
volume = {27},
number = {1},
pages = {78},
pmid = {41540303},
issn = {1530-9932},
mesh = {*Alzheimer Disease/drug therapy/metabolism ; Humans ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism/drug effects ; Animals ; Nanoparticles/chemistry ; Brain/metabolism/drug effects ; Amyloid beta-Peptides/metabolism ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognitive functions. It represents a global health concern with increasing prevalence and devastating outcomes for the quality of life that could ultimately lead to death. AD is associated with deposition of β-amyloid (Aβ) plaques and intracellular buildup of tau proteins forming neurofibrillary tangles (NFTs), which are the main characteristics for AD brain tissues. Approved AD therapy is based mainly on symptomatic relief, and conventional medicaments often fail due to either low bioavailability, limited solubility, or failure to cross blood-brain barrier (BBB). The complexity in AD pathophysiology opens windows for many therapeutic options. So, lecanemab was recently approved by FDA as the first disease-modifying therapy. However, drug delivery to the brain remains challenging due to the nature of BBB. Hence, more extensive research is essential to develop disease-modifying therapies and also to find drug delivery strategies to ensure simplified administration and successful brain delivery. This review article summarizes AD pathogenesis with the corresponding treatment targets. It emphasizes innovative drug delivery strategies and novel formulation approaches to deliver medicines across BBB. The use of recent advancements in drug delivery to deliver medicaments across BBB are highlighted, with focus given to novel drug delivery systems and formulation of nanoparticles for brain targeting. The use of nutraceuticals, gene therapy, and stem cell therapy are is covered.},
}

*Alzheimer Disease/drug therapy/metabolism
Humans
*Drug Delivery Systems/methods
Blood-Brain Barrier/metabolism/drug effects
Animals
Nanoparticles/chemistry
Brain/metabolism/drug effects
Amyloid beta-Peptides/metabolism

@article {pmid41540243,
year = {2026},
author = {Vanderlinden, G and Vandenbulcke, M and Van Laere, K},
title = {High-resolution [[18]F]MK-6240 PET in Alzheimer's disease.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41540243},
issn = {1619-7089},
support = {FWO/G093218N//Fonds Wetenschappelijk Onderzoek/ ; 1292326N//Fonds Wetenschappelijk Onderzoek/ ; C24-17-063//Onderzoeksraad, KU Leuven/ ; },
}

@article {pmid41540118,
year = {2026},
author = {Zhao, S and Toniolo, S and Tang, QY and Scholcz, A and Ganse-Dumrath, A and Gendarini, C and John Broulidakis, M and Thompson, S and Manohar, SG and Husain, M},
title = {Remote digital cognitive assessment for aging and dementia using the Oxford Cognitive Testing Portal OCTAL.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02346-6},
pmid = {41540118},
issn = {2398-6352},
support = {226645/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; 226645/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; 226645/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; 226645/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; 226645/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; 226645/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; MR/P00878/X/MRC_/Medical Research Council/United Kingdom ; },
abstract = {The global rise in dementia necessitates scalable cognitive assessments that can evolve to serve both clinical and research applications. We present the Oxford Cognitive Testing Portal (OCTAL), a remote, browser-based platform providing performance metrics for memory, attention, visuospatial and executive function domains. Four validation studies (N = 1664) confirmed cross-cultural applicability, lifespan sensitivity and clinical utility. Task performance was equivalent in English- and Chinese-speaking younger adults and mapped domain-specific ageing trajectories in mid- to late-adulthood. In a memory-clinic cohort (N = 194), 5-minute OCTAL screen distinguished patients with Alzheimer's disease dementia from subjective cognitive decline (AUC = 0.92), matching a standard paper-based test, while a 20-minute subset surpassed this (AUC = 0.97; p = 0.04). Test-retest reliability was very good (ICC ≥ 0.79; N = 118). OCTAL enables remote assessment for large-scale research and screening, with an open, modular architecture that makes it a uniquely sustainable and evolvable tool for the research community.},
}

@article {pmid41540008,
year = {2026},
author = {Vervliet, T and Loncke, J and Sever, M and Ahuja, K and Van den Haute, C and Luyten, T and Stutzmann, GE and Verfaillie, C and Tomašič, T and Bultynck, G},
title = {Inactive ryanodine receptors sustain lysosomal availability for autophagy by promoting ER-lysosomal contact site formation.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-68054-z},
pmid = {41540008},
issn = {2041-1723},
support = {12ZG121N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; 209833/1S03424N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; FWO-SBO-S001221N-OrganID//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; G081821N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; P1-0208//The Slovenian Research and Innovation Agency (ARIS)/ ; P1-0208//The Slovenian Research and Innovation Agency (ARIS)/ ; },
abstract = {Lysosomal and endoplasmic reticulum (ER) Ca[2+] release mutually influence each other's functions. Recent work revealed that ER-located ryanodine receptor(s) (RyR(s)) Ca[2+] release channels suppress autophagosome turnover by the lysosomes. In familial Alzheimer's disease, inhibiting RyR hyperactivity restored autophagic flux by normalizing lysosomal vacuolar H[+]-ATPase (vATPase) levels. However, the mechanisms by which RyRs control lysosomal function and how this involves the vATPase remain unknown. Here, we show that RyRs interact with the ATP6v0a1 subunit of the vATPase, contributing to ER-lysosomal contact site formation. This interaction suppresses RyR-mediated Ca[2+] release, leading to reduced lysosomal exocytosis. Pharmacological inhibition of RyR activity mimics these effects on lysosomal exocytosis. Retaining lysosomes inside cells via RyR inhibition increases ER-lysosomal contact site formation, rendering lysosomes more available for autophagic flux. In summary, these findings establish RyR/ATP6v0a1 complexes as ER-lysosomal tethers that dynamically and Ca[2+] dependently regulate the intracellular availability of lysosomes to participate in autophagic flux.},
}

@article {pmid41539787,
year = {2026},
author = {Luo, A and Zhao, Q and Zhang, X and Chen, J and Liu, Q and Huang, R and Zheng, Q and Zhong, S},
title = {Delivery systems for betalains: from stabilization strategies to precision nutrition applications.},
journal = {Food research international (Ottawa, Ont.)},
volume = {226},
number = {},
pages = {118095},
doi = {10.1016/j.foodres.2025.118095},
pmid = {41539787},
issn = {1873-7145},
mesh = {*Betalains/chemistry/administration & dosage ; Humans ; *Drug Delivery Systems/methods ; Biological Availability ; Antioxidants/administration & dosage/chemistry ; Nanoparticles ; *Precision Medicine ; Liposomes ; Emulsions ; },
abstract = {Betalains are natural, water-soluble, nitrogen-containing pigments that have attracted widespread attention due to their potent antioxidant, anti-inflammatory, and other beneficial physiological properties. However, their poor environmental stability and low bioavailability pose considerable challenges to their broader application in the food industry. Therefore, there is an urgent need to develop effective strategies to protect betalains from degradation under environmental stressess while simultaneously enhancing their bioavailability to maximize their health benefits in nutrition intervention. This review focuses on the design and fabrication of various betalain-based delivery systems, including emulsions, liposomes, nanoparticles, microcapsules, and hydrogels. Additionally, it highlights the potential benefits of betalains-based delivery systems in precision nutrition, which include recognizing individual-specific signals to achieve targeted release and nutritional interventions for cancer, diabetes, and Alzheimer's disease. Finally, the future prospects and challenges of betalains-based delivery systems in the field of precision nutrition are discussed. In conclusion, these technological advancements enable targeted delivery to specific patient populations, thereby maximizing the therapeutic efficacy of betalains through precisely engineered delivery systems. This approach support tailored nutritional interventions for a variety of diseases and address the various requirements of precision nutrition for special populations.},
}

*Betalains/chemistry/administration & dosage
Humans
*Drug Delivery Systems/methods
Biological Availability
Antioxidants/administration & dosage/chemistry
Nanoparticles
*Precision Medicine
Liposomes
Emulsions

@article {pmid41539753,
year = {2026},
author = {Jing, L and Zhang, Z and Zhang, Z and Xu, Y and Tian, J and Fu, X and Yu, L and Chen, J and Ma, J},
title = {Hydroxysafflor yellow A from safflower enhances stress resilience and proteostasis in Caenorhabditis elegans.},
journal = {Food research international (Ottawa, Ont.)},
volume = {226},
number = {},
pages = {118100},
doi = {10.1016/j.foodres.2025.118100},
pmid = {41539753},
issn = {1873-7145},
mesh = {Animals ; *Caenorhabditis elegans/drug effects/metabolism ; *Quinones/pharmacology ; *Carthamus tinctorius/chemistry ; *Chalcone/analogs & derivatives/pharmacology ; *Proteostasis/drug effects ; Caenorhabditis elegans Proteins/metabolism/genetics ; Oxidative Stress/drug effects ; Longevity/drug effects ; Reactive Oxygen Species/metabolism ; Heat-Shock Proteins/metabolism ; Superoxide Dismutase/metabolism ; Forkhead Transcription Factors/metabolism ; Autophagy/drug effects ; Antioxidants/pharmacology ; Unfolded Protein Response/drug effects ; Transcription Factors ; },
abstract = {Dietary bioactive compounds from edible plants are increasingly recognized for their roles in promoting healthy aging and protecting against stress-induced cellular damage. Hydroxysafflor yellow A (HSYA), a water-soluble chalcone glycoside abundant in safflower (Carthamus tinctorius L.), is widely used as a natural pigment and has emerging potential as a functional food ingredient. Here, we investigated the effects of HSYA on lifespan and stress resistance using Caenorhabditis elegans (C. elegans). HSYA significantly extended lifespan by up to 78 % under heat stress, 29.03 % under oxidative stress, and also 8.49 % under normal conditions. Mechanistic studies showed that HSYA enhanced DAF-16 nuclear translocation, upregulated HSF-1 and heat shock proteins (HSP), and activated unfolded protein response and autophagy pathways, thereby preserving proteostasis. In addition, HSYA strengthened defenses, reduced reactive oxygen species, and increased the activity of superoxide dismutase (SOD), peroxidase (POD) activities, and glutathione-S-transferase (GST). Importantly, HSYA alleviated toxic protein aggregation in Alzheimer's- and Parkinson's-like worm models, delaying paralysis and supporting neuronal health. Collectively, these findings demonstrate that HSYA exerts dual antioxidant and proteostasis-regulating activities in vivo, highlighting its promise as a plant-derived dietary bioactive with potential applications in functional foods targeting aging and age-related disorders.},
}

Animals
*Caenorhabditis elegans/drug effects/metabolism
*Quinones/pharmacology
*Carthamus tinctorius/chemistry
*Chalcone/analogs & derivatives/pharmacology
*Proteostasis/drug effects
Caenorhabditis elegans Proteins/metabolism/genetics
Oxidative Stress/drug effects
Longevity/drug effects
Reactive Oxygen Species/metabolism
Heat-Shock Proteins/metabolism
Superoxide Dismutase/metabolism
Forkhead Transcription Factors/metabolism
Autophagy/drug effects
Antioxidants/pharmacology
Unfolded Protein Response/drug effects
Transcription Factors

@article {pmid41539591,
year = {2026},
author = {Pravin, V and Vellapandian, C and Naveen Kumar, V},
title = {The oral-gut-brain axis in periodontitis: microbial signaling in systemic and neuroinflammatory disease.},
journal = {Brain research},
volume = {},
number = {},
pages = {150168},
doi = {10.1016/j.brainres.2026.150168},
pmid = {41539591},
issn = {1872-6240},
abstract = {Periodontitis, a chronic inflammatory disease of the oral cavity, has been identified as a modifiable risk factor of the development of systemic and neurological disorders via a complicated interplay of microbiological, immunological, and neural interactions. Periodontal pathogens breach local immune homeostasis, are translocated to the gut and brain, and trigger a cascade of immune deregulation, leaky gut, and blood-brain barrier, thereby forming a tri-directional communication network that links local oral inflammation to systemic and neurovascular conditions. This review synthesizes existing evidence on how oral dysbiosis, can spread to the gut and trigger systemic inflammation, leading to neuroinflammation and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Mechanistically, the OGB axis acts through various processes, such as hematogenous spread, retrograde axonal transport, immune cell trafficking (Trojan horse mechanism), and extracellular vesicle-based signaling corresponding to the causes of neuroinflammation, microglial activation, and the pathology of tau and amyloid. The diagnostic and therapeutic implications of the OGB axis provide new pathways toward early intervention with precision medicine, microbiome remodeling, immune-based therapy, and neuroprotective approaches. Emerging technologies, including AI-based diagnostics and biosensing technologies, offers noninvasive tools to track host-microbial interactions and inflammatory biomarkers. This integrative view underscores the central importance of oral health in systemic homeostasis and the development of neurodegenerative conditions, necessitating collaborative approaches between dentistry, neurology, and immunology to cooperate to deliver efficacy in disease elimination and mitigation.},
}

@article {pmid41539579,
year = {2026},
author = {Yin, Q and Hu, M and Li, W and Cheng, P and Liu, Y and Liu, L and Chen, L and Ru, Q and Wu, Y},
title = {Alkaloids and flavonoids of Solanaceae: Mechanisms of action in neurodegenerative diseases.},
journal = {Brain research bulletin},
volume = {235},
number = {},
pages = {111716},
doi = {10.1016/j.brainresbull.2026.111716},
pmid = {41539579},
issn = {1873-2747},
abstract = {Neurodegenerative diseases (e.g., Alzheimer's disease [AD], Parkinson's disease [PD], Huntington's disease [HD]) pose a serious threat to human health. Current therapeutic approaches have limitations such as significant side effects and limited efficacy, making natural plant active ingredients an emerging research focus in this field. Solanaceae plants are widely distributed worldwide, rich in secondary metabolites such as alkaloids and flavonoids, and have long been used in traditional medicine. This review systematically summarizes the structural characteristics of Solanaceae-derived alkaloids (e.g., nicotine[NI], atropine[ATP], scopolamine[SCO]) and flavonoids (e.g., quercetin[QR], luteolin[LUT], kaempferol[KAE], anthocyanidin[ACN]), as well as their therapeutic potential and core mechanisms of action against the three major neurodegenerative diseases - including multi-target regulatory pathways such as antioxidative stress, inhibiting neuroinflammation, regulating neurotransmitter balance, preventing abnormal protein aggregation, and suppressing neuronal apoptosis. Additionally, this review analyzes the challenges faced by these natural products in extraction and purification, bioavailability, target selectivity, and clinical translation, and prospects the potential of promoting their clinical application through technological breakthroughs such as synthetic biology and nanodelivery systems. This review indicates that Solanaceae-derived secondary metabolites provide an important resource for the development of safe and effective therapeutic drugs for neurodegenerative diseases, with broad application value.},
}

@article {pmid41539516,
year = {2026},
author = {Xu, H and Zheng, Y and Bai, G and Wang, Y and Ma, B},
title = {Differential conformational selections of three therapeutic antibodies binding to polymorphic Aβ oligomers.},
journal = {International journal of biological macromolecules},
volume = {341},
number = {Pt 1},
pages = {150222},
doi = {10.1016/j.ijbiomac.2026.150222},
pmid = {41539516},
issn = {1879-0003},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) aggregates, which play a central role in disease pathogenesis according to the amyloid cascade hypothesis. While soluble Aβ oligomers and protofibrils have been identified as the most neurotoxic species, their structural heterogeneity has posed significant challenges for therapeutic development. Current antibody therapies targeting Aβ show differential clinical efficacy, but the molecular basis for their selective recognition of various Aβ polymorphs remains unclear. This critical knowledge gap stems from the lack of experimental structures of antibody-oligomer complexes, which hinders rational drug design. In this study, we thoroughly simulated possible interactions between Aβ oligomer and three antibodies recently approved for targeting Aβ as AD therapy. Our results reveal fundamental differences in their recognition mechanisms. Aducanumab shows polymorph-dependent binding, targeting N-terminal epitopes in full-length Aβ but maintaining non-specific contacts to cross-β structures. Lecanemab uniquely engages multiple N-termini simultaneously through an extended flat-binding interface. Donanemab employs a conserved CDRL1-dominated mode to recognize F4-H13 aggregates, with the pE3 modification acting as a structural anchor that reinforces binding stability. These structural insights provide a molecular basis for observed clinical outcomes and establish design principles for improved therapeutics targeting specific pathological aggregates.},
}

@article {pmid41539445,
year = {2026},
author = {Huang, J and Rehman, H and Doan, C and Stein, TD and Mez, J and Ang, TFA and Tao, Q and Au, R and Farrer, LA and Zhang, X and Qiu, WQ},
title = {Circulating C-reactive protein influences polygenic risk of inflammatory genes expressed in brain endothelia for Alzheimer's disease.},
journal = {Neurobiology of disease},
volume = {219},
number = {},
pages = {107257},
doi = {10.1016/j.nbd.2026.107257},
pmid = {41539445},
issn = {1095-953X},
abstract = {BACKGROUND: C-reactive protein (CRP) is a key marker of systemic inflammation that affects blood vessel endothelial function, including in the brain. Since endothelial dysfunction is linked to Alzheimer's disease (AD), we investigated whether elevated CRP level interacts with genetic pathways in brain endothelial cells to influence AD risk.

METHODS: Using AD genome-wide association study (GWAS) data, we developed multiple polygenic risk scores (PRSs) including single nucleotide polymorphisms (SNPs) in genes expressed in brain endothelial cells, excluding the APOE region, that are involved in inflammation, synaptic transmission, and other pathways.

RESULTS: Analysis across three independent cohorts revealed that individuals with low inflammatory PRSs (<50%) and elevated blood CRP level were associated with an increased risk of AD; in contrast, those with high inflammatory PRSs (≥50%) did not exhibit this CRP-related AD risk increase. Further examination of individuals with a low inflammatory PRS showed that elevated CRP was associated with lower cerebrospinal fluid (CSF) Aβ42 level and temporal lobe atrophy. Among individuals with a high inflammatory PRS, elevated CRP level was negatively correlated with CSF pTau181 and brain tauopathy, suggesting a potential protective mechanism against tau pathology. Key inflammatory PRS genes, which were impacted by circulating CRP for AD, included APP, IL6ST, and FN1, are involved in amyloid pathology, wound healing, and coagulation.

CONCLUSION: Our findings highlight two distinct genetic-dose dependent backgrounds: "vulnerable" (<50% inflammatory PRS) and "resilient" (≥50% inflammatory PRS), and support a Genome-Internal Environment (G×IE) interaction model, linking peripheral inflammation to AD risk.},
}

@article {pmid41539386,
year = {2026},
author = {Hector, A and Leduc, T and Caiado, MJDC and Delignat-Lavaud, B and Dufort-Gervais, J and Daneault, C and Des Rosiers, C and Bourguignon, C and Lina, JM and Fernandes, K and Brouillette, J and Mongrain, V},
title = {Electrocorticographic, Astrocytic and Transcriptomic Signatures in the Triple Transgenic Mouse Model of Alzheimer's Disease submitted to Stearoyl-CoA Desaturase Inhibition.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110835},
doi = {10.1016/j.neuropharm.2026.110835},
pmid = {41539386},
issn = {1873-7064},
abstract = {Alzheimer's disease (AD) is associated with cognitive deficits and sleep disturbances. Research suggests the involvement of dysfunctions in lipid metabolism in the brain of AD patients and animal models. The inhibition of stearoyl-CoA desaturase (SCD), a lipid-converting enzyme, was shown to restore memory in triple transgenic (3xTg)-AD mice. In the brain, astrocytes regulate the synthesis of specific lipids. This project tested whether the inhibition of SCD restores sleep in 3xTg-AD mice, and whether this associates with modifications in lipids, astrocytic function and the transcriptome. Wild-type (WT) and 3xTg-AD female mice received a SCD inhibitor (SCDi) or vehicle, which was followed by an electrocorticographic (ECoG) recording. Brain slices were stained for lipid droplets, astrocytic markers or processed for spatial transcriptomics. The reduced time spent awake (increased time spent in slow wave sleep) in 3xTg-AD mice was not restored by SCDi treatment. Rhythmic and scale-free ECoG activities were markedly altered in 3xTg-AD mice for all wake/sleep states, and SCDi changed these ECoG signatures differently in mutant in comparison to WT mice. GFAP-positive cell density and lipid droplet count were elevated in hippocampal CA1, and rescued by SCDi. The treatment also rescued the expression of several genes in a manner mainly overlapping between brain regions. The findings suggest that the multiple wake/sleep alterations in 3xTg-AD mice are not mitigated by SCD inhibition, but that this treatment can revert changes in hippocampal astrocytes, lipids and in the brain transcriptome. This work will benefit the understanding of the AD pathophysiology and associated sleep disturbances.},
}

@article {pmid41539204,
year = {2026},
author = {Li, Y and Lagier, RJ and Racke, MK and Fesko, YA},
title = {Cost-effectiveness analysis of blood-based biomarker testing in the diagnosis of Alzheimer's disease pathology.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {3},
pages = {100474},
doi = {10.1016/j.tjpad.2025.100474},
pmid = {41539204},
issn = {2426-0266},
abstract = {OBJECTIVES: We aimed to evaluate the cost-effectiveness of blood-based biomarker (BBM) testing vs amyloid positron emission tomography (PET) in patients with signs and symptoms of cognitive decline in a neurologist/specialist care setting.

METHODS: We constructed a decision-tree model to compare diagnostic outcomes and costs of two testing strategies: BBM testing with confirmatory PET scan vs PET scan alone. Their cost-effectiveness was evaluated from a payer perspective with test performance taken from a clinical study and costs including testing/imaging and physician fees.

RESULTS: When access to PET scans is unlimited, BBM triage testing would identify 98.2 % of PET+ patients with a lower average cost per diagnosis compared with PET scan alone ($8868 vs 10,345 per PET+ diagnosis). In terms of incremental cost-effectiveness, BBM triage testing would save $93,984 for each loss of PET+ diagnosis (9.1 times the average cost per PET+ diagnosis by PET scan). Under limited capacity of PET scans, more test-positive patients could be identified using BBM testing than PET scan alone. When access to PET scans is limited to 50 % of the patients, BBM testing would identify 90.6 % more test-positive patients (at 93 % sensitivity) at an incremental cost-effectiveness ratio of $3484 per gain of positive diagnosis, lower than the average cost of a PET+ diagnosis by PET scan ($10,938).

CONCLUSION: BBM testing, compared with PET scan alone, is more efficient in the utilization of available amyloid PET scans and is cost-effective for assessment of Alzheimer's disease pathology in patients with signs and symptoms of cognitive decline.},
}

@article {pmid41539185,
year = {2026},
author = {Zhang, S and Jiao, B and Zeng, Y and Sun, Q and Chen, X and Zhang, W and Ouyang, Z and Xiao, Q and Zhou, L and Li, Y and Weng, L and Du, J and Xu, Q and Yang, Y and Zhang, M and Zeng, Q and Fang, L and Long, H and Xie, Y and Chen, S and Feng, L and Huang, Q and Long, L and Zhou, Y and Yi, F and Hu, Y and Liu, Q and Pan, Y and Zhou, L and Li, Y and Hu, S and Guo, J and Wang, J and Jiang, H and Xu, H and Duan, R and Tang, B and Tian, Y and Shen, L},
title = {Plasma p-tau species are elevated in presymptomatic and symptomatic neuronal intranuclear inclusion disease.},
journal = {EBioMedicine},
volume = {124},
number = {},
pages = {106127},
doi = {10.1016/j.ebiom.2026.106127},
pmid = {41539185},
issn = {2352-3964},
abstract = {BACKGROUND: Neuronal intranuclear inclusion disease (NIID), caused by GGC repeat expansions in NOTCH2NLC, is a neurodegenerative disease frequently involved with cognitive impairment. Limited studies have focused on the biomarkers alteration in patients with NIID and presymptomatic NIID (preNIID) individuals. The clinical overlap between NIID and AD drives the exploration of plasma biomarker alterations in NIID and preNIID.

METHODS: Cohorts 1 (87 patients with NIID, 147 individuals with Alzheimer's disease [AD], and 110 healthy controls [HCs]) and 2 (26 individuals with preNIID and 26 HCs) were included. Eight plasma biomarkers including amyloid-β (Aβ) 40, Aβ42, neurofilament light (NfL), α-synuclein (α-syn), phosphorylated tau protein 181 (p-tau181), p-tau217, p-tau231, and glial fibrillary acidic protein (GFAP) were detected. Neuropsychological scores, magnetic resonance imaging measures, Aβ positron emission tomography (Aβ-PET), and tau-PET were analysed.

FINDINGS: P-tau217, p-tau231, p-tau181, α-syn, NfL, and GFAP levels were elevated in patients with NIID compared with HCs; p-tau species and GFAP were also upregulated in preNIID. P-tau species, particularly p-tau217, effectively distinguished NIID/preNIID from HCs (AUC 0.814/0.848), but failed to differentiate NIID from AD. The level of p-tau217 was associated with MMSE and FAB scores in dementia-dominant subtype, and the level of GFAP correlated to white matter volume. A tau-PET study revealed distinct tau deposition on the occipital lobe and temporal pole in NIID without Aβ pathology.

INTERPRETATION: The significant changes of p-tau levels and prominent tau deposition highlight tau pathology involvement in NIID. Elevated plasma p-tau species in preNIID/NIID indicate their potential as biomarkers for NIID.

FUNDING: This study was supported by the National Natural Science Foundation of China (82394421, 82394420, 82371866, 82371434); the National Key R&D Program of China (2022ZD0213700); Natural Science Foundation of Hunan Province (2023JJ10097, 2025JJ40089, 2023JJ40948).},
}

@article {pmid41539164,
year = {2025},
author = {Öztürk, NK and Akünal, C},
title = {The role of the MIND diet in Alzheimer's disease patients: A case-control study on malnutrition and depression.},
journal = {Nutrition (Burbank, Los Angeles County, Calif.)},
volume = {144},
number = {},
pages = {113077},
doi = {10.1016/j.nut.2025.113077},
pmid = {41539164},
issn = {1873-1244},
abstract = {OBJECTIVE: The aim of this study was to examine the association between depression, malnutrition, and the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet in Alzheimer's disease patients.

METHODS: This study included 30 patients with Alzheimer's disease (AD) and 30 healthy controls. A questionnaire form including sociodemographic characteristics was applied to the individuals. In addition, anthropometric measurements, biochemical parameters, nutritional status (Food Frequency Questionnaire (FFQ), Mini Nutritional Assessment-Short Form (MNA-SF), Geriatric Nutritional Risk Index (GNRI) and MIND diet scores) and mental health status [Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI)].

RESULTS: BDI and BAI scores were significantly higher in the AD group compared to the control group. MIND diet score was found to be significantly lower in the AD group compared to the control group (independent t-tests, P < 0.05). Higher adherence to the MIND diet was significantly associated with lower malnutrition and depression scores among Alzheimer's disease patients (correlation analyses, P < 0.05). The risk of developing AD was found to be 2.034 times higher in those with high malnutrition status (logistic regression analysis, 95% CI; 1.143-3.621; P = 0.016, R[2]: 44.2%). Those with a high MIND diet score had an approximately 2.879-fold increased chance of being healthy (logistic regression analysis, 95% CI; 1.506-5.503; P = 0.001, R[2]: 44.2%). According to ROC analysis, the area under the curve (AUC) for the depression score was 0.946 (P < 0.001).

CONCLUSIONS: These findings suggest that adherence to the MIND diet may support nutrition and psychological well-being in AD and highlight the value of integrating nutrition-based approaches into dementia care.},
}

@article {pmid41539110,
year = {2026},
author = {Shrivastav, K and Pandey, M and Gor, H and Nema, V},
title = {Gut virome plays an extended role with bacteriome in neurological health and disease.},
journal = {Journal of the neurological sciences},
volume = {481},
number = {},
pages = {125754},
doi = {10.1016/j.jns.2026.125754},
pmid = {41539110},
issn = {1878-5883},
abstract = {The gut-brain axis (GBA) is a complex two-way communication system that links the gastrointestinal tract and the central nervous system (CNS) through neural, immune, hormonal, and microbial pathways. The microbiota-gut-brain axis (MGBA), a more specific concept, focuses on how gut microorganisms, including bacteria, viruses, and other microbes, modulate this communication and influence neurological health. This comprehensive review examines the intricate mechanisms through which gut microorganisms modulate neural function and contribute to neurological health and disease pathogenesis. The gut microbiota, comprising bacteria, viruses, fungi, and bacteriophages, produces essential neuroactive compounds including neurotransmitters- Gamma-Aminobutyric Acid (GABA), serotonin (5-HT), dopamine (DA), short-chain fatty acids (SCFAs), and metabolites that directly influence brain physiology through vagal, hormonal, and immunological pathways. Dysbiosis of the gut microbiota has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorders, and schizophrenia. In healthy conditions, beneficial bacterial strains such as Lactobacillus species synthesize GABA and regulate mood, while SCFA-producing bacteria like Fecalibacterium prausnitzii maintain blood-brain barrier integrity and exert neuroprotective effects. Conversely, pathological states demonstrate altered microbial compositions, reduced bacterial diversity, and compromised production of beneficial metabolites. Emerging evidence highlights the previously underexplored role of the gut virome, particularly bacteriophages, in regulating bacterial populations and influencing neurodevelopment. Viral dysbiosis correlates with cognitive impairment and neurodegenerative processes through modulation of bacterial metabolism and inflammatory responses. Understanding these complex host-microbiome-virome interactions provides novel therapeutic opportunities for neurological disorders through targeted interventions including probiotics, fecal microbiota transplantation, and phage-based therapies, representing a paradigm shift toward microbiome-centered approaches in neurological medicine.},
}

@article {pmid41539103,
year = {2026},
author = {Shi, R and Li, Y and Mou, L and Zheng, Y and Xia, L and Liu, Y and Stoika, R and Sik, A and Liu, K and Jin, M},
title = {Unraveling the Anti-Alzheimer's mechanisms of optimal constituent from Arisaema heterophyllum Blume through multi-model and phytochemical analysis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {151},
number = {},
pages = {157813},
doi = {10.1016/j.phymed.2026.157813},
pmid = {41539103},
issn = {1618-095X},
abstract = {BACKGROUND: Alzheimer's disease (AD) is one of the most significant health threats globally, with limited therapeutic options currently available. Arisaema heterophyllum Blume (AhBl), a traditional Chinese herb, has been used as a medicine for centuries, yet its neuroprotective effects toward AD have not been systematically studied.

PURPOSE: This study aimed to evaluate the anti-AD effects and pharmacological mechanisms of AhBl ethanol extracts (EE), as well as to identify the optimal active constituent.

METHODS AND RESULTS: AhBl EE significantly alleviated AD-like symptoms. The 2:1 MeOH/DCM elution fraction showed the most potent activity, improving dyskinesia, reducing cerebral amyloid-β (Aβ) deposition and neuronal apoptosis, inhibiting acetylcholinesterase activity, and mitigating blood-brain barrier (BBB) leakage. Through integrated phytochemical characterization, bioinformatic prediction, and pharmacological evaluation, the linoleic acid was identified as the optimal active constituent. In addition to alleviating AD-like symptoms in zebrafish larvae, the linoleic acid exhibited similar effects in the AD model in adult zebrafish, improving preference, learning and memory, and exploratory abilities. Furthermore, it significantly restored abnormal gene expression in the regulation of learning and memory, as well as in BBB and cholinergic system functions. In cellular AD models, the linoleic acid enhanced Aβ clearance and promoted a shift from pro-inflammatory M1 to anti-inflammatory M2 microglial polarization, confirming its anti-AD action. These findings suggest that the mechanism of the linoleic acid action involves reversing BBB disruption, thereby preventing the effect of neurotoxins such as Aβ from damaging cholinergic neurons and subsequently slowing AD progression.

CONCLUSIONS: Our findings demonstrated for the first time that the linoleic acid is an optimal anti-AD active constituent of AhBl. Its basic mechanisms involve reversing BBB disruption and protecting cholinergic neurons from damage, thereby supporting its potential as a promising candidate for AD therapy.},
}

@article {pmid41537925,
year = {2026},
author = {Cheng, Y and Santucci, K and Gao, Y and Takenaka, K and Lindner, G and Xu, SM and Janitz, M},
title = {Utilisation of Machine Learning Approaches Improves RNA-Seq Transcriptome Analyses in Alzheimer's Disease Brain.},
journal = {Journal of molecular neuroscience : MN},
volume = {76},
number = {1},
pages = {9},
pmid = {41537925},
issn = {1559-1166},
abstract = {UNLABELLED: Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively deteriorates a person’s memory, as well as their ability to think and move. It has been reported to be the most common cause of dementia. Alterations in gene expression have been increasingly recognised as key contributors to the onset and progression of AD, driving interest in transcriptomic approaches to better understand the disease at a molecular level. The development of machine learning (ML) approaches in transcriptomics have been rapid in the past decade, and this advancement can be applied to the study of AD transcriptomes. An ML program that enhances the alignment data through filtering out low confidence splice junction reads, Splam, has been developed by Chao et al. (2023). However, this program has not been utilised and assessed in the transcriptomic study of a complex neurological disease such as AD. This study investigates both the transcriptome of AD brain and the potential of an ML program to enhance alignment-stage data quality and influence downstream analyses. Using the Integrative Genomics Viewer, a selection of filtered reads was visualised, uncovering the types of splice junction reads Splam discards to refine the alignment data. From the differential expression (DE) analysis, we found a higher number of DE transcripts using ML-filtered data compared to unfiltered data, potentially unmasking aspects of AD brain DE profile obscured by alignment noise. The gene loci expressing those transcripts were also determined to be more AD-relevant by comparing these findings with external studies, and contribute to more related gene ontology enrichment terms. We identified gene loci expressing transcripts of interest shared between ML-filtered and unfiltered data, as this consistency in detection suggests that these genes are robust candidates for downstream analyses and biomarkers in AD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12031-025-02469-7.},
}

@article {pmid41537783,
year = {2026},
author = {Wang, C and Zhang, H and Jiao, F and Huang, F and Li, C and Men, J and Ju, Z and Lin, H and Yang, Y and Lu, J and Yue, C and Jiang, W and Zhang, S and Wang, M and Guan, Y and Gao, X and Zuo, C and Jiang, J},
title = {Stratifying amyloid burden in early Alzheimer's disease using cascaded attention-guided vision transformer using [[18]F]Florbetapir PET.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {41537783},
issn = {1432-1084},
support = {62376150//National Natural Science Foundation of China/ ; 2022ZD021606//Science and Technology Innovation 2030 - Major Projects/ ; SHU-UM-JBGS-2025-8//Digital Medical Research Institute Research Funding-Shanghai University/ ; },
abstract = {OBJECTIVES: This study aims to develop a deep learning model to assist physicians in accurately classifying negative, equivocal, and positive β-amyloid (Aβ) deposition stages in Alzheimer's disease (AD).

MATERIALS AND METHODS: 1327 subjects from two cohorts underwent [¹⁸F]Florbetapir PET and were grouped by Aβ deposition. A cascaded attention-guided vision transformer (CA-ViT) framework was proposed to extract biologically significant regional information for fine-grained classification. To evaluate clinical utility, we assessed the diagnostic performance of physicians with and without the assistance of our proposed method.

RESULTS: The CA-ViT model demonstrated outstanding cross-center performance, achieving accuracies of 82.8% [79.1%, 86.5%] (96% confidence interval, CI) and 78.0% [75.1%, 80.9%] in three-class classification tasks in the two cohorts, respectively. Our proposed model-assisted physicians exhibited significant improvements in diagnostic accuracy (from 56% to 66% and from 50% to 77%).

CONCLUSION: The CA-ViT model effectively decodes fine-grained pathological information from [¹⁸F]Florbetapir PET imaging, enabling accurate stratification of Aβ deposition to assist physicians in early monitoring of AD.

KEY POINTS: Question Deep learning has the potential to assist physicians in accurately classifying β-amyloid deposition stages in early Alzheimer's disease. Findings The proposed diagnostic model is a promising computer-aided tool for early assessment of amyloid deposition and demonstrates improved physician performance. Clinical relevance Equivocal amyloid deposition often complicates early Alzheimer's disease diagnosis and may delay optimal interventions. Our model, validated on PET scans from multiple centers, enhances the identification of these equivocal cases and improves diagnostic accuracy among less-experienced physicians.},
}

@article {pmid41537773,
year = {2026},
author = {},
title = {Correction to "Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model".},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e19668},
doi = {10.1002/advs.202519668},
pmid = {41537773},
issn = {2198-3844},
}

@article {pmid41537771,
year = {2026},
author = {Wang, N and Sun, Z and Chen, F and Tian, X and Li, J and He, X},
title = {Mangiferin Alleviates Formaldehyde-Induced Tau Hyperphosphorylation and Cognitive Impairment in Mice via the PI3K/AKT/GSK3β Pathway: Insights From Network Pharmacology and Experimental Validation.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {2},
pages = {e71346},
doi = {10.1096/fj.202503159R},
pmid = {41537771},
issn = {1530-6860},
support = {202401AT070082//Yunnan Fundamental Research Projects/ ; 202301BA070001-032//Yunnan Fundamental Research Projects/ ; },
mesh = {Animals ; *Glycogen Synthase Kinase 3 beta/metabolism ; Mice ; *tau Proteins/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; *Cognitive Dysfunction/chemically induced/metabolism/drug therapy ; *Phosphatidylinositol 3-Kinases/metabolism ; *Xanthones/pharmacology ; Phosphorylation/drug effects ; Male ; Network Pharmacology/methods ; *Formaldehyde/toxicity ; Molecular Docking Simulation ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Hippocampus/metabolism/drug effects ; },
abstract = {Studies have demonstrated that accumulation of formaldehyde (FA) in the body can result in Alzheimer's disease (AD) like changes including cognitive impairment, Aβ deposition, and Tau hyperphosphorylation. Mangiferin (MGF), a natural flavonoid compound, has been suggested in previous reports to have potential in the treatment of AD. This study integrated network pharmacology and in vivo experiments to elucidate the therapeutic potential and mechanisms of MGF in mitigating FA-induced neurotoxicity. Potential overlapping targets between MGF and AD were identified using jvenn. Functional enrichment analysis of these targets was performed with DAVID. A protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape to identify hub genes. Molecular docking simulations with AutoDock were then employed to assess binding affinity. Subsequently, for experimental validation, a mouse model of FA-induced neurotoxicity was established. Spatial memory and cognitive function in mice were evaluated using the Y-maze and novel object recognition tests. The expression levels of key pathway-related proteins in the cortex and hippocampus were analyzed via immunohistochemistry (IHC) and Western blotting (WB). Network analysis identified AKT1 and GSK3β as key targets, and molecular docking confirmed strong binding affinity between MGF and these proteins. Experimental validation demonstrated that MGF dose-dependently improved spatial memory and cognitive performance in FA-exposed mice, reduced neuronal apoptosis, and suppressed Tau hyperphosphorylation at Thr181, Ser396, and Ser404. Mechanistically, MGF activated the PI3K/AKT pathway, leading to GSK3β inactivation through Ser9 phosphorylation. These findings highlight MGF as a promising therapeutic candidate for AD by targeting the PI3K/AKT/GSK3β axis.},
}

Animals
*Glycogen Synthase Kinase 3 beta/metabolism
Mice
*tau Proteins/metabolism
*Proto-Oncogene Proteins c-akt/metabolism
*Cognitive Dysfunction/chemically induced/metabolism/drug therapy
*Phosphatidylinositol 3-Kinases/metabolism
*Xanthones/pharmacology
Phosphorylation/drug effects
Male
Network Pharmacology/methods
*Formaldehyde/toxicity
Molecular Docking Simulation
Signal Transduction/drug effects
Mice, Inbred C57BL
Hippocampus/metabolism/drug effects

@article {pmid41538772,
year = {2026},
author = {Liao, YS and Wai, T and Liao, TY and Chang, HL and Chang, YL and Fu, LC},
title = {Mild Cognitive Impairment Detection System Based on Unstructured Spontaneous Speech: Longitudinal Dual-Modal Framework.},
journal = {JMIR medical informatics},
volume = {14},
number = {},
pages = {e80883},
pmid = {41538772},
issn = {2291-9694},
mesh = {Humans ; *Cognitive Dysfunction/diagnosis ; Aged ; Male ; Female ; Longitudinal Studies ; *Speech ; Aged, 80 and over ; Memory, Episodic ; China ; },
abstract = {BACKGROUND: In recent years, the incidence of cognitive diseases has also risen with the significant increase in population aging. Among these diseases, Alzheimer disease constitutes a substantial proportion, placing a high-cost burden on health care systems. To give early treatment and slow the progression of patient deterioration, it is crucial to diagnose mild cognitive impairment (MCI), a transitional stage.

OBJECTIVE: In this study, we use autobiographical memory (AM) test speech data to establish a dual-modal longitudinal cognitive detection system for MCI. The AM test is a psychological assessment method that evaluates the cognitive status of subjects as they freely narrate important life experiences.

METHODS: Identifying hidden disease-related information in unstructured, spontaneous speech is more difficult than in structured speech. To improve this process, we use both speech and text data, which provide more clues about a person's cognitive state. In addition, to track how cognition changes over time in spontaneous speech, we introduce an aging trajectory module. This module uses local and global alignment loss functions to better learn time-related features by aligning cognitive changes across different time points.

RESULTS: In our experiments on the Chinese dataset, the longitudinal model incorporating the aging trajectory module achieved area under the receiver operating characteristic curve of 0.85 and 0.89 on 2 datasets, respectively, showing significant improvement over cross-sectional, single time point models. We also conducted ablation studies to verify the necessity of the proposed aging trajectory module. To confirm that the model not only applies to AM test data, we used part of the model to evaluate the performance on the ADReSSo dataset, a single time point semistructured data for validation, with results showing an accuracy exceeding 0.88.

CONCLUSIONS: This study presents a noninvasive and scalable approach for early MCI detection by leveraging AM speech data across multiple time points. Through dual-modal analysis and the introduction of an aging trajectory module, our system effectively captures cognitive decline trends over time. Experimental results demonstrate the method's robustness and generalizability, highlighting its potential for real-world, long-term cognitive monitoring.},
}

Humans
*Cognitive Dysfunction/diagnosis
Aged
Male
Female
Longitudinal Studies
*Speech
Aged, 80 and over
Memory, Episodic
China

@article {pmid41538578,
year = {2026},
author = {Khan, M and Saeed, U and Piracha, ZZ and Ozsahin, I and Shao-Chun, C},
title = {Innovative public-health strategies for neurodegenerative disease: leveraging diversified ultraviolet irradiation as a next-generation therapy.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {85},
number = {},
pages = {e297765},
doi = {10.1590/1519-6984.297765},
pmid = {41538578},
issn = {1678-4375},
mesh = {Humans ; *Neurodegenerative Diseases/radiotherapy/therapy ; *Ultraviolet Therapy/methods ; *Ultraviolet Rays ; *Public Health ; Oxidative Stress/radiation effects ; },
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis are escalating worldwide, straining healthcare systems and leaving patients with therapies that are largely palliative. Emerging evidence positions diversified ultraviolet (UV) irradiation as a groundbreaking, non-invasive strategy to counter these disorders. Beyond its traditional use in sterilization, specific UV spectra, UV-B (280-320 nm), UV-C (200-280 nm), and far-UV (207-222 nm), are now recognized for modulating oxidative stress, restoring mitochondrial function, correcting apoptotic dysregulation, and enhancing DNA repair. Innovative approaches such as riboflavin-mediated phototherapy and photobiomodulation (PBM) show the capacity to disaggregate toxic protein aggregates like β-amyloid and α-synuclein, boost antioxidant defenses, stimulate neurotrophic factors, and quell neuroinflammation. Preclinical models and early clinical trials reveal preserved cognition, enhanced neurogenesis, and reduced disease biomarkers, suggesting real translational promise. From a public-health perspective, UV-based interventions offer a cost-effective, scalable option for aging populations and resource-limited settings, especially when integrated with community-level health technologies and remote delivery platforms. Continued investigation of optimal dosing, long-term safety, and mechanistic pathways will be pivotal to unlock the full therapeutic and population-wide impact of this novel modality.},
}

Humans
*Neurodegenerative Diseases/radiotherapy/therapy
*Ultraviolet Therapy/methods
*Ultraviolet Rays
*Public Health
Oxidative Stress/radiation effects

@article {pmid41538324,
year = {2026},
author = {Dunn, LN and Niemeyer, BF and Eduthan, NP and Schade, KA and Waugh, KA and Brown, C and Rachubinski, AL and Timkovich, AE and Orlicky, DJ and Galbraith, MD and Espinosa, JM and Sullivan, KD},
title = {Altered hepatic metabolism in Down syndrome.},
journal = {Cell reports},
volume = {45},
number = {1},
pages = {116835},
doi = {10.1016/j.celrep.2025.116835},
pmid = {41538324},
issn = {2211-1247},
abstract = {Trisomy 21 (T21) gives rise to Down syndrome (DS), the most commonly occurring chromosomal abnormality in humans. T21 affects nearly every organ and tissue system in the body, predisposing individuals with DS to congenital heart defects, autoimmunity, and Alzheimer's disease, among other co-occurring conditions. Here, using multi-omic analysis of plasma from more than 400 people, we report broad metabolic changes in the population with DS typified by increased bile acid levels and protein signatures of liver dysfunction. In a mouse model of DS, we demonstrate conservation of perturbed bile acid metabolism accompanied by liver pathology. Bulk RNA sequencing revealed widespread impacts of the Dp16 model on hepatic metabolism and inflammation, while single-cell transcriptomics highlighted cell types associated with these observations. Modulation of dietary fat profoundly impacted gene expression, bile acids, and liver pathology. Overall, these data represent evidence for altered hepatic metabolism in DS that could be modulated by diet.},
}

@article {pmid41537514,
year = {2025},
author = {McGoldrick, KE},
title = {Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's.},
journal = {Anesthesiology},
volume = {143},
number = {6},
pages = {1672-1673},
pmid = {41537514},
issn = {1528-1175},
}

@article {pmid41537461,
year = {2026},
author = {Choi, KY and Kang, S and Cook, S and Li, D and Choi, YY and Seo, EH and Han, X and Park, JE and Lee, S and Lee, S and Chung, JY and Chong, A and Choi, SM and Ha, JM and Song, MK and Lee, JS and Choo, IH and Kim, JH and Song, HC and Kim, BC and Kim, H and Farrer, LA and Gim, J and Jun, GR and Lee, KH},
title = {The Gwangju Alzheimer's & Related Dementias (GARD) cohort: Over a decade of Asia's largest longitudinal multimodal study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70981},
pmid = {41537461},
issn = {1552-5279},
support = {25-BR-03-05//the KBRI Basic Research Program through the Korea Brain Research Institute, funded by the Ministry of Science and ICT/ ; NRF-2014M3C7A1046041//the Original Technology Research Program for Brain Science of the National Research Foundation funded by the Korean government, MSIT/ ; RS-2024-00407198//Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea/ ; 2023-ER1007-01//Korea National Institute of Health research project/ ; //by the Technology Innovation Program (20022810, Development and Demonstration of a Digital System for the evaluation of geriatric Cognitive impairment) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea)/ ; RS-2024-00433283//the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy, Republic of Korea/ ; HR22C141105//Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea/ ; },
mesh = {Humans ; Longitudinal Studies ; Male ; *Alzheimer Disease/epidemiology/diagnostic imaging/genetics/diagnosis ; Female ; Aged ; *Cognitive Dysfunction/epidemiology/diagnostic imaging ; Disease Progression ; Republic of Korea/epidemiology ; Cohort Studies ; Middle Aged ; Biomarkers ; Magnetic Resonance Imaging ; Aged, 80 and over ; Neuroimaging ; Proteomics ; Genomics ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a major public health concern in Korea, with a high prevalence among older adults. A community-based longitudinal study is essential for tracking disease progression, identifying biomarkers, and developing targeted prevention and treatment strategies. The Gwangju Alzheimer's & Related Dementias (GARD) cohort was established to address these needs through a multimodal approach.

METHODS: Participants aged ≥60 years undergo comprehensive clinical evaluations, neuroimaging, and biospecimen collection for multi-omics analyses (genomics, transcriptomics, proteomics, and metagenomics) at baseline and systematic follow-up visits.

RESULTS: From over 17,000 screened individuals, 12,877 were enrolled. Baseline diagnoses include 5,123 cognitively unimpaired (CU), 3,250 mild cognitive impairment (MCI), and 2,125 AD dementia. The resource includes magnetic resonance imaging scans (n = 10,843) and extensive multi-omics data: genomic (n = 10,775), proteomic (n = 116), and microbiome (n = 595).

DISCUSSION: The integrated GARD dataset provides a powerful and scalable resource for identifying novel biomarkers, understanding disease heterogeneity, and advancing precision medicine for AD.

HIGHLIGHTS: Gwangju Alzheimer's & Related Dementias (GARD) is a large-scale, longitudinal, community-based cohort study in South Korea. The study focuses on early detection and monitoring of dementia progression. GARD includes cognitive testing, imaging, biospecimens, and multi-omics data. We aim to identify Korean-specific biomarkers predictive of cognitive decline. Supports East Asian insights and fills gaps in global Alzheimer's research.},
}

Humans
Longitudinal Studies
Male
*Alzheimer Disease/epidemiology/diagnostic imaging/genetics/diagnosis
Female
Aged
*Cognitive Dysfunction/epidemiology/diagnostic imaging
Disease Progression
Republic of Korea/epidemiology
Cohort Studies
Middle Aged
Biomarkers
Magnetic Resonance Imaging
Aged, 80 and over
Neuroimaging
Proteomics
Genomics

@article {pmid41537459,
year = {2026},
author = {Ren, J and Pan, W},
title = {Large-Scale Genotype-Based Trait Imputation With Multi-Ancestry GWAS Data.},
journal = {Genetic epidemiology},
volume = {50},
number = {1},
pages = {e70030},
pmid = {41537459},
issn = {1098-2272},
support = {U01 AG073079/NH/NIH HHS/United States ; R01 AG065636/NH/NIH HHS/United States ; RF1 AG067924/NH/NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study/methods ; Alzheimer Disease/genetics ; Genotype ; Polymorphism, Single Nucleotide ; Models, Genetic ; Phenotype ; United Kingdom ; White People/genetics ; },
abstract = {Genome-wide association studies (GWAS) have been instrumental in identifying genetic variants associated with complex traits and diseases, including Alzheimer's disease (AD). However, traditional GWAS approaches often focus on European populations, which may lead to loss of power and limit the generalizability of findings across diverse ancestries. On the other hand, LS-Imputation, a nonparametric trait imputation method, leverages GWAS summary statistics and genotype data to impute missing traits, which can then be used for GWAS and other downstream analyses. Although LS-Imputation has been applied successfully to European populations, its performance in non-European populations would be hindered by smaller sample sizes, leading to reduced imputation accuracy. To address these limitations, we propose two novel variants of LS-Imputation-LS-Imputation-Combined and LS-Imputation-Transfer-designed to integrate multi-ancestry GWAS data and enhance imputation performance. LS-Imputation-Combined optimally combines GWAS summary statistics from multiple ancestries, while LS-Imputation-Transfer sequentially refines imputed trait values across ancestries using stochastic gradient descent. We evaluate these methods using data from the UK Biobank and the Alzheimer's Disease Sequencing Project (ADSP), first applying them to high-density lipoprotein (HDL) cholesterol levels as a proof-of-concept before focusing on imputing AD status in Black individuals for genetic association analysis. Our results demonstrate that integrating multi-ancestry GWAS data improves trait imputation accuracy, with LS-Imputation-Transfer achieving the highest performance.},
}

Humans
*Genome-Wide Association Study/methods
Alzheimer Disease/genetics
Genotype
Polymorphism, Single Nucleotide
Models, Genetic
Phenotype
United Kingdom
White People/genetics

@article {pmid41537452,
year = {2026},
author = {Herd, P and Sicinski, K and Williams, V and Asthana, S and Engelman, M},
title = {Early-life influences on the risk for later-life Alzheimer's and non-Alzheimer's dementia: A nearly full life course prospective cohort study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e70967},
pmid = {41537452},
issn = {1552-5279},
support = {/NH/NIH HHS/United States ; 2R01AG060737//National Institute on Aging "Initial Lifetime Incidence of Alzheimer's Disease in the Wisconsin Longitudinal Study/ ; R24AG077433//"Network on Education, Biosocial Pathways, and Dementia across Populations/ ; R24AG077433/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/epidemiology ; Female ; Male ; Risk Factors ; Prospective Studies ; Educational Status ; Longitudinal Studies ; Aged ; *Dementia/epidemiology ; Cognitive Reserve ; Wisconsin/epidemiology ; Aged, 80 and over ; Middle Aged ; Cohort Studies ; },
abstract = {BACKGROUND: Dementia prevention research has largely used educational attainment as a proxy for early-life. Given the known influence of early-life exposures on brain development, more attention to early-life exposures is warranted.

METHODS: We employ the Wisconsin Longitudinal Study, a nearly full life course cohort study, to examine the influence of prospectively measured early-life risk factors for dementia in later life.

RESULTS: We find that early-life risk factors that precede high school completion, rather than early adulthood post-secondary schooling, exert influence on later-life dementia. Household parental resources influence non-Alzheimer's disease (AD), but not AD, dementia risk. In contrast, markers for adolescent cognitive reserve (cognitive and academic performance measures) influence AD dementia risk, in part, by modifying genetic risk.

DISCUSSION: Using education as a proxy for early-life exposures conceals specific mechanisms that influence distinct dementia etiologies and are separately intervenable. Education's influence may be confined to the early-life and adolescent period, where brain development is especially malleable.

HIGHLIGHTS: Educational attainment is commonly used as a proxy for early-life risk factors for dementia. Given known early-life influences on brain development, more attention to the period is warranted. Early-life parental income influences non-AD dementia risk. Early-life cognition and academic performance influence AD dementia risk. Using educational attainment as a proxy for early-life exposures conceals separate intervenable risk factors.},
}

Humans
*Alzheimer Disease/epidemiology
Female
Male
Risk Factors
Prospective Studies
Educational Status
Longitudinal Studies
Aged
*Dementia/epidemiology
Cognitive Reserve
Wisconsin/epidemiology
Aged, 80 and over
Middle Aged
Cohort Studies

@article {pmid41537429,
year = {2026},
author = {Zhang, S and Liesz, A},
title = {Trained immunity in acute and chronic neurological diseases.},
journal = {eLife},
volume = {15},
number = {},
pages = {},
pmid = {41537429},
issn = {2050-084X},
support = {EXC 2145 SyNergy//German Research Foundation/ ; Consolidator GRANT TRAINED ID 101229857/ERC_/European Research Council/International ; },
mesh = {Humans ; *Immunity, Innate ; *Nervous System Diseases/immunology ; Animals ; Chronic Disease ; Brain/immunology/pathology ; Acute Disease ; Trained Immunity ; },
abstract = {Trained immunity, the long-term reprogramming of innate immune cells to elicit an enhanced response upon subsequent challenges, has become a key concept in understanding a wide range of pathologies, including both acute and chronic inflammatory disorders. Recent evidence suggests that trained immunity also plays a significant role in the development and progression of various neurological disorders and related comorbidities, in which brain pathology can lead to trained immunity. This review summarizes the current understanding of trained immunity within both brain-resident immune cells and myeloid-derived innate immune cells, focusing on their roles in neurological disorders, such as ischemic brain injury, Parkinson's disease, and Alzheimer's disease. Additionally, we explore the heterogeneity of trained immunity across different conditions and its potential applications in clinical neurology.},
}

Humans
*Immunity, Innate
*Nervous System Diseases/immunology
Animals
Chronic Disease
Brain/immunology/pathology
Acute Disease
Trained Immunity

@article {pmid41537338,
year = {2026},
author = {Hibar, DP and Bauer, A and Rabe, C and Borlinghaus, N and Jethwa, A and Kollmorgen, G and Di Domenico, A and Zetterberg, H and Blennow, K and Masters, CL and Sperling, RA and Bittner, T},
title = {Elecsys pTau217 plasma immunoassay detection of amyloid pathology in clinical cohorts.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71009},
pmid = {41537338},
issn = {1552-5279},
support = {#2023-00356//Swedish Research Council/ ; #2022-01018//Swedish Research Council/ ; #2019-02397//Swedish Research Council/ ; 101053962//European Union's Horizon Europe Research and Innovation Programme/ ; #ALFGBG-71320//Swedish State Support for Clinical Research/ ; //F. Hoffmann-La Roche Ltd./ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Alzheimer Disease/blood/diagnosis ; *Amyloid beta-Peptides ; Biomarkers/blood ; *Cognitive Dysfunction/blood/diagnosis ; Cohort Studies ; Immunoassay/methods ; Phosphorylation ; Positron-Emission Tomography ; *tau Proteins/blood ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Clinical Trials, Phase III as Topic ; },
abstract = {INTRODUCTION: We evaluated the clinical performance of the fully automated, high-throughput, prototype Elecsys[®] Phospho-Tau (217P) plasma immunoassay (Roche Diagnostics) for detecting amyloid pathology.

METHODS: Plasma tau phosphorylated at threonine 217 (pTau217) levels were determined in samples from cognitively impaired and unimpaired individuals from five cohorts (N = 2148) using the pTau217 plasma immunoassay. Clinical performance was evaluated against amyloid positron emission tomography.

RESULTS: For cognitively impaired, mean plasma pTau217 levels for amyloid-positive (A+) individuals were higher (n = 394; 0.835 pg/mL) than amyloid-negative (A-) individuals (n = 144; 0.361 pg/mL); similarly, for cognitively unimpaired, A+ (n = 224; 0.516 pg/mL) and A- individuals (n = 1386; 0.220 pg/mL). Area under the curve was 0.878 (95% confidence interval [CI] 0.840, 0.915; impaired) and 0.907 (95% CI 0.885, 0.929; unimpaired). A cutoff < 0.189 pg/mL reliably ruled out individuals without amyloid pathology. High negative predictive values (92.51% [impaired]; 98.60% [unimpaired]) were observed with sensitivity/specificity of 98.98%/29.17% and 95.54%/50.72%, respectively.

DISCUSSION: The pTau217 plasma immunoassay accurately detects amyloid pathology, irrespective of cognitive status.

TRIAL REGISTRATION NUMBER: A4, NCT02008357; SKYLINE, NCT05256134; AIBL, SAGE Project ID Number: 2022/PID06188; SVHM Local Ref ID: HREC 028/06; CREAD, NCT02670083; CREAD2, NCT03114657 HIGHLIGHTS: The Elecsys[®] pTau217 plasma immunoassay (Roche Diagnostics) was evaluated across five cohorts. The pTau217 plasma immunoassay demonstrated high performance in detecting amyloid pathology in both cognitively impaired and unimpaired individuals. The pTau217 plasma immunoassay had a high negative predictive value which supports its utility as a pre-screening tool for Alzheimer's disease (AD). The pTau217 plasma immunoassay cutoffs identified are suitable for use as rule-out pre-screener tools in clinical trials. These findings reinforce the value of the high-throughput pTau217 plasma immunoassay measurements to aid AD diagnosis.},
}

Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
*Alzheimer Disease/blood/diagnosis
*Amyloid beta-Peptides
Biomarkers/blood
*Cognitive Dysfunction/blood/diagnosis
Cohort Studies
Immunoassay/methods
Phosphorylation
Positron-Emission Tomography
*tau Proteins/blood
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Clinical Trials, Phase III as Topic

@article {pmid41537308,
year = {2026},
author = {Yao, M and Tian, P and Li, X and Bian, S and Wang, G and Gu, Y and Navas-Acien, A and Vardarajan, BN and Belsky, DW and Miller, GW and Baccarelli, AA and Liu, Z},
title = {CoxMDS: multiple data splitting for high-dimensional mediation analysis with survival outcomes in epigenome-wide studies.},
journal = {Briefings in bioinformatics},
volume = {27},
number = {1},
pages = {},
pmid = {41537308},
issn = {1477-4054},
support = {R01AG086379/NH/NIH HHS/United States ; },
mesh = {Humans ; *DNA Methylation ; Lung Neoplasms/genetics/mortality ; *Epigenome ; CpG Islands ; Proportional Hazards Models ; Alzheimer Disease/genetics/mortality ; *Epigenomics/methods ; Survival Analysis ; Genome-Wide Association Study ; Smoking/genetics/adverse effects ; *Mediation Analysis ; },
abstract = {Causal mediation analysis investigates whether the effect of an exposure on an outcome operates through intermediate variables known as mediators. Although progress has been made in high-dimensional mediation analysis, current methods do not reliably control the false discovery rate (FDR) in finite samples, especially when mediators are moderately to highly correlated or follow non-Gaussian distributions. These challenges frequently arise in DNA methylation studies. We introduce CoxMDS, a multiple data splitting method that uses Cox proportional hazards models to identify putative causal mediators for survival outcomes. CoxMDS ensures finite-sample FDR control even in the presence of correlated or non-Gaussian mediators. Through simulations, CoxMDS is shown to maintain FDR control and achieve higher statistical power compared with existing approaches. In applications to DNA methylation data with survival outcomes, CoxMDS identified eight CpG sites in The Cancer Genome Atlas that are consistent with the hypothesis that DNA methylation may mediate the effect of smoking on lung cancer survival, and two CpG sites in the Alzheimer's Disease Neuroimaging Initiative that are consistent with the hypothesis that DNA methylation may mediate the effect of smoking on time to Alzheimer's disease conversion.},
}

Humans
*DNA Methylation
Lung Neoplasms/genetics/mortality
*Epigenome
CpG Islands
Proportional Hazards Models
Alzheimer Disease/genetics/mortality
*Epigenomics/methods
Survival Analysis
Genome-Wide Association Study
Smoking/genetics/adverse effects
*Mediation Analysis

@article {pmid41536850,
year = {2026},
author = {Okhravi, HR and Fang, F and Hunter, MP and Sheehan, BE},
title = {Effect of antipsychotic medication use and type on mortality and cardiovascular risks in nursing home patients with dementia.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70247},
pmid = {41536850},
issn = {2352-8729},
abstract = {INTRODUCTION: Antipsychotic medication (APM) use in nursing home (NH) patients with dementia is common but carries risks. This study assessed the association between APM use and mortality, stroke, and myocardial infarction (MI) compared to non-use, as well as differences between first- and second-generation APMs.

METHODS: A serial cross-sectional study using Medicare data examined outcomes from 2012 to 2015 in a national sample of 328,138 US NH residents aged 50 and older with dementia. Multivariate logistic regressions were used to analyze risk.

RESULTS: APM use was associated with increased mortality in all years (odds ratio [OR] range: 2.39 to 1.23, all p < 0.001) and stroke risk from 2012 to 2014 (OR range: 1.17 to 1.10, p < 0.01) but not MI. First-generation APMs posed a higher mortality risk than second-generation APMs, with no significant stroke or MI differences.

DISCUSSION: Findings highlight the need for cautious APM use in dementia patients in NHs due to elevated mortality and stroke risks.

HIGHLIGHTS: Study provides insights into APM risks in underrepresented nursing home (NH) dementia population.APM use in NH dementia patients is linked to higher death risk.First-generation APMs showed higher mortality risk than second-generation APMs.Overall, APM use is associated with increased stroke risk.No association was found between APM use and MI risk overall.},
}

@article {pmid41536849,
year = {2026},
author = {Nakashima, S and Sato, K and Niimi, Y and Ihara, R and Ikeuchi, T and Ishii, K and Ito, K and Iwata, A and Kasuga, K and Kato, T and Kowa, H and Nakase, T and Senda, M and Suzuki, K and Tomita, N and Tsukamoto, T and Yoshiyama, K and Toda, T and Iwatsubo, T},
title = {Characterizing Japanese older adults without dementia by amyloid PET status: A comparative study of amyloid-positive and amyloid-negative groups from Japanese trial-ready cohort study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70242},
pmid = {41536849},
issn = {2352-8729},
abstract = {INTRODUCTION: This study aimed to identify demographic and cognitive differences based on amyloid status in older Japanese adults without dementia, addressing the lack of data in East Asian populations for early Alzheimer's disease (AD) detection.

METHODS: Analyzed baseline data from 630 participants from the Japanese Trial-Ready Cohort (J-TRC) study, all with a Clinical Dementia Rating-Global Score (CDR-GS) of 0 or 0.5. Amyloid status (Aβ+ or Aβ-) was determined by amyloid positron emission tomography (PET) scans.

RESULTS: Among participants, 24.8% were Aβ+. In the cognitively unimpaired (CDR-GS 0) group, Aβ+ individuals reported slightly greater self-perceived cognitive concerns (Cognitive Function Instrument [CFI-self]). For those with mild impairment (CDR-GS 0.5), Aβ+ status was associated with worse clinical scores, greater cognitive complaints, more depressive symptoms, and poorer memory and global cognition.

DISCUSSION: These findings align with major Western studies, emphasizing that CFI-self is a valuable tool for identifying early AD pathology across diverse populations.

HIGHLIGHTS: Comparing characteristics by amyloid status in Japanese non-demented older adults.Positron emission tomography-positive (PET+) scans in cognitively unimpaired individuals were associated with Cognitive Function Instrument-negative (CFI-) participants.PET+ in mild cognitive impairment (MCI) was linked to functional, cognitive, and affective decline.CFI- participants will aid early Alzheimer's pathology detection in diverse groups.},
}

@article {pmid41536772,
year = {2025},
author = {He, C and Zhou, Y and Chen, Y and Jing, Y},
title = {Research on interpretable machine learning models for diagnosis and staging of mild cognitive impairment.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1708525},
pmid = {41536772},
issn = {1664-2295},
abstract = {BACKGROUND: Mild cognitive impairment (MCI) is a critical prodromal stage of Alzheimer's disease (AD), further categorized into early MCI (EMCI) and late MCI (LMCI). Early and accurate diagnosis is essential for effective prevention and intervention of AD. This study aims to develop an accessible and interpretable machine learning model to facilitate early diagnosis and subtype staging of MCI.

METHODS: A total of 268 participants were recruited from the ADNI, including cognitively normal individuals (CN, n = 132), EMCI (n = 95), and LMCI (n = 41). Participants were randomly divided into training (80%) and testing (20%) cohorts. Multimodal data encompassing whole-brain T1-WI MRI radiomics, clinical neuropsychological scales and plasma protein biomarkers were collected. Logistic regression (LR) and random forest (RF) algorithms were employed to construct six unimodal models based on above three categories of features, as well as a combined model combining all features. Diagnostic performance for the three-class classification task (CN, EMCI, LMCI) was evaluated using receiver operating characteristic (ROC) curve. Furthermore, SHapley Additive exPlanations (SHAP) were applied to quantify the contribution of individual features within the integrated model.

RESULTS: The combined model significantly outperformed unimodal models across all metrics, achieving macro_AUC = 0.92, micro_AUC = 0.91, and ACC = 0.81 in the training set, and macro_AUC = 0.87, micro_AUC = 0.87, and ACC = 0.76 in the testing set. The LR-based radiomics model ranked second. Models based solely on clinical neuropsychological scales or plasma protein biomarkers demonstrated comparatively lower classification performance. SHAP analysis highlighted neuropsychological scales (ADAS-Cog, MoCA) and radiomic features from critical brain regions (hippocampus, middle temporal gyrus, entorhinal cortex) as pivotal contributors to model efficacy.

CONCLUSION: The integration of whole-brain structural MRI (sMRI) radiomics, neuropsychological scales, and plasma protein biomarkers significantly improves the precision of diagnosing and staging mild cognitive impairment (MCI). Radiomic characteristics derived from critical cerebral regions yield valuable pathological information that facilitates clinical interpretation. This methodology presents a promising strategy for the early identification and individualized management of MCI.},
}

@article {pmid41536422,
year = {2025},
author = {Thaliath, A and Pillai, JA},
title = {Non-Cognitive Symptoms in Alzheimer's Disease and Their Likely Impact on Patient Outcomes. A Scoping Review.},
journal = {Current treatment options in neurology},
volume = {27},
number = {},
pages = {},
pmid = {41536422},
issn = {1092-8480},
support = {P30 AG072959/AG/NIA NIH HHS/United States ; },
abstract = {PURPOSE OF REVIEW: Increased understanding of the pathophysiology of Alzheimer's disease (AD) has led to development of disease modifying therapies. The therapies primarily target measures of cognitive decline since AD has been thought of as a cognitive disorder. However, the non-cognitive symptoms seen in AD contribute to overall quality-of-life. This scoping review was undertaken to further our understanding of the non-cognitive features of AD.

RECENT FINDINGS: The non-cognitive symptoms in AD range from changes in sensory perception, systemic changes, and neuropsychiatric manifestations. We targeted the following non-cognitive domains: vision, olfaction, GI, muscle, sleep, circadian rhythm, immune and behavioral symptoms as it relates to AD for this review. Non-cognitive features impact the ability of individuals to perform their activities of daily living, have safety implications and lead to increased caregiver burden. The review explores non-pharmacological and pharmacological measures targeted at the non-cognitive changes in AD.

SUMMARY: Non-cognitive symptoms contribute to significant disease burden in Alzheimer's disease. It is important to screen for and provide supportive care for these symptoms to help improve clinical care. Incorporation of non-cognitive features of AD in clinical trials will help ascertain the true societal and economic impact of AD and that of potential therapeutics.

OPINION STATEMENT: Alzheimer's disease (AD) is primarily recognized as a disorder of cognition; however, non-cognitive symptoms significantly contribute to disease burden and clinical presentation. These manifestations particularly behavioral symptoms and systemic changes beyond the central nervous system impact patients' quality of life and increase caregiver stress. Often, such symptoms necessitate a transition from home-based care to more intensive settings, such as memory care facilities. As AD prevalence rises alongside an aging population, the shortage of dedicated memory care providers in community settings challenges access and quality of care. Improved awareness and early recognition of non-cognitive features among healthcare professionals can aid identification of modifiable systemic issues and allow timely behavioral management during clinical encounters. Treatment of these symptoms requires a multifaceted approach, incorporating pharmacological and non-pharmacological strategies. Non-pharmacological interventions, including tailored behavioral approaches and environmental modifications, can enhance quality of life for individuals with AD and reduce caregiver burden especially where specialized medical resources are limited.},
}