@article {pmid42258677,
year = {2026},
author = {Yin, M and Ravindran, KKG and Hadjipanayi, C and Bannon, A and Monica, CD and Rapeaux, A and Lande, TS and Dijk, DJ and Constandinou, T},
title = {Using Legacy Polysomnography Data to Train a Radar System to Quantify Sleep in Older Adults and People living with Dementia.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3701134},
pmid = {42258677},
issn = {1558-2531},
abstract = {OBJECTIVE: Ultra-wideband (UWB) radar technology offers a promising solution for unobtrusive and cost-effective in-home sleep monitoring. However, the limited availability of radar sleep data poses challenges in building robust models that generalize across diverse cohorts and environments. This study proposes a novel deep transfer learning framework to enhance sleep stage classification using radar data.

METHODS: An end-to-end neural network was developed to classify sleep stages based on nocturnal respiratory and motion signals. The network was trained using a combination of large-scale polysomnography (PSG) datasets and radar data. A domain adaptation approach employing adversarial learning was utilized to bridge the knowledge gap between PSG and radar signals. Validation was performed on a radar dataset of 47 older adults (mean age: 71.2 ± 6.5), including 18 participants with prodromal or mild Alzheimer's disease.

RESULTS: The proposed network structure achieves an accuracy of 79.5% with a Kappa value of 0.65 when classifying wakefulness, rapid eye movement, light sleep and deep sleep. Experimental results confirm that our deep transfer learning approach significantly enhances automatic sleep staging performance in the target domain.

CONCLUSION: This method effectively addresses challenges associated with data variability and limited sample size, substantially improving the reliability of automatic sleep staging models, especially in contexts where radar data is limited.

SIGNIFICANCE: The findings underscore the viability of UWB radar as a nonintrusive, forward-looking sleep assessment tool that could significantly benefit care for older people and people with neurodegenerative disorders.},
}

@article {pmid42259020,
year = {2026},
author = {López-Martos, D and Cacciaglia, R and Suárez-Calvet, M and Salvadó, G and Shekari, M and González-Escalante, A and Milà-Alomà, M and Brugulat-Serrat, A and Minguillon, C and Tonietto, M and Borroni, E and Klein, G and Quijano-Rubio, C and Kollmorgen, G and Zetterberg, H and Blennow, K and Gispert, JD and Grau-Rivera, O and Sánchez-Benavides, G and , },
title = {Multimodal biomarker characterization of amnestic objective subtle cognitive decline in aging and preclinical Alzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {7},
pages = {100612},
doi = {10.1016/j.tjpad.2026.100612},
pmid = {42259020},
issn = {2426-0266},
abstract = {BACKGROUND: The objective of this study was to provide a multimodal biomarker characterization of amnestic objective subtle cognitive decline (obj-SCD) in aging and preclinical Alzheimer's disease (AD).

METHODS: Prospective observational study; data from the Alzheimer's and Families+ (ALFAs+) cohort, including cognitively unimpaired (CU) individuals with available baseline CSF biomarkers (normal or AD continuum profiles) and longitudinal neuropsychological assessment (2 time points, 3-year follow-up). Amnestic obj-SCD was defined using robust longitudinal neuropsychological references with multivariate base rate thresholds of significant decline (Free and Cued Selective Reminding Test, Memory Binding Test, Wechsler Memory Scale IV: Logical Memory). Study outcomes included plasma p-tau217, NfL, and GFAP; CSF p-tau181/Aβ42, NfL, and GFAP; Aβ and tau PET; and MRI Grey Matter volume (GMv). The associations of amnestic obj-SCD with fluid (plasma and CSF) and neuroimaging biomarkers (PET and GMv) were evaluated using mixed-effects and voxel-wise linear regression models, respectively.

RESULTS: 350 CU individuals were included (mean age 61 years; 60% female; mean education 14 years; 35% CSF Aβ-positive). Amnestic obj-SCD was identified in 10% of the sample, associated with greater AD pathology (higher plasma p-tau217, CSF p-tau181/Aβ42, global Aβ PET, medial temporal tau PET), neurodegeneration (higher plasma and CSF NfL, reduced GMv in cingulate cortex, longitudinal GMv reductions in hippocampus) and inflammation (higher plasma and CSF GFAP, longitudinal GMv increases in neocortical brain regions).

DISCUSSION: These findings highlight the need for standardized clinical staging criteria to enhance early detection and risk stratification in aging and preclinical AD.},
}

@article {pmid42259049,
year = {2026},
author = {Wang, C and Song, X and Chen, D and Su, J and Wang, Y and Huang, C and Wei, W},
title = {Gold-nanocube-based SERS sensor for accurate detection of Alzheimer's disease biomarkers: Aβ42 and MAO-B.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {362},
number = {},
pages = {128185},
doi = {10.1016/j.saa.2026.128185},
pmid = {42259049},
issn = {1873-3557},
abstract = {Considering the irreversible nature of Alzheimer's disease (AD), early diagnosis is of great importance for AD treatment. Both β-amyloid (Aβ) and monoamine oxidase B (MAO-B) are potential biomarkers for AD. This study developed a surface-enhanced Raman scattering (SERS) sensor using gold-nanocube (OX-AuNCs) to detect Aβ42 and MAO-B. OX-AuNCs, a type of gold-nanocube with open gaps, achieved a Raman enhancement factor of 8.99 × 10[8] due to numerous hot spots. The specific affinity between Thioflavin T (ThT) and Aβ42 inhibits ThT's intramolecular rotation, reducing its SERS signal. This reduced signal showed a linear correlation with Aβ42 concentrations from 66.70 pM to 0.20 μM, achieving a limit of detection (LOD) at 44.30 pM, while also distinguishing different aggregation levels of Aβ42. Interestingly, SERS intensity of phenethylamine (PEA) also decreased significantly when interacting with MAO-B. A linear relationship was found between the change in PEA intensity and MAO-B concentration (0.01-20.00 μg mL[-1]), yielding an LOD of 5.00 ng mL[-1]. The proposed SERS sensor effectively detected two potential AD biomarkers, Aβ42 and MAO-B, in artificial cerebrospinal fluid (ACSF) and human serum with satisfactory recovery rates, respectively. These results show promise for clinical diagnosis and drug screening for AD.},
}

@article {pmid42259141,
year = {2026},
author = {Alnsour, L and Al-Samydai, A and Sadek, B and Akour, A},
title = {Repurposing antidiabetics for Alzheimer's disease and related neurodegenerative disorders: Translational challenges and role of nanoparticle-mediated CNS targeting.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {200},
number = {},
pages = {119614},
doi = {10.1016/j.biopha.2026.119614},
pmid = {42259141},
issn = {1950-6007},
abstract = {Diabetes mellitus has been linked to cognitive impairment and Alzheimer's disease (AD). They share common pathologic pathways, including insulin resistance, mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation. These shared mechanisms have prompted interest in repurposing antidiabetic agents as promising therapies for neurodegenerative diseases. Despite this overlap, these drugs face translational challenges, primarily due to their poor penetration across the blood-brain barrier (BBB) and, consequently, poor central nervous system (CNS) bioavailability. Nanoparticle-based drug delivery offers an alternative route to improve targeting of the CNS by increasing the drug stability and augmenting transport across the BBB. Although preclinical evidence showed promising results, the extent to which these findings translate into clinically tangible outcomes remains uncertain. This review critically evaluates the main preclinical studies on nanoparticle-mediated delivery of antidiabetic agents, with particular emphasis on AD and diabetes-associated cognitive impairment, where most available data are concentrated. We also discuss the main brain-targeting strategies, their limitations, and the translational challenges to their clinical application, particularly for conditions beyond AD, where the evidence remains sparse. Addressing these barriers is crucial for the development of nanomedicine-based approaches from bench to bedside. This review provides a critical standpoint on the field and highlights priorities for future research aimed at the effective translation of nanoparticle-enabled therapies for neurodegenerative diseases.},
}

@article {pmid42259196,
year = {2026},
author = {Yao, W and Qu, M and Deng, C and Zhang, C and Zhang, X and Hu, X and Zhang, J and Yang, T and Liu, F and Wang, T and Li, D and Wang, X},
title = {Bacteria-derived equol alleviates Aβ toxicity in C. elegans through PEK-1-associated UPRer activation.},
journal = {Biochemical and biophysical research communications},
volume = {828},
number = {},
pages = {154071},
doi = {10.1016/j.bbrc.2026.154071},
pmid = {42259196},
issn = {1090-2104},
abstract = {Alzheimer's disease (AD) is the leading cause of dementia with no effective disease-modifying treatments. Here, we found that Escherichia coli (E. coli) DH5α relieved learning defects and paralysis, and prolonged lifespan in amyloid-β (Aβ)-expressing C. elegans. DH5α inhibited Aβ aggregation via activating the PEK-1-dependent endoplasmic reticulum unfolded protein response (UPRer). We further identified equol from DH5α metabolites, which alleviated AD-related phenotypes through the same PEK-1/UPRer pathway.},
}

@article {pmid42259394,
year = {2026},
author = {Zhang, K and Kong, S and Ma, Y and Kan, C and Zheng, T and Sun, X},
title = {Natural Monomer Compounds in Neurodegenerative Diseases: Targeting Ferroptosis and Neuroinflammation.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116319},
doi = {10.1016/j.bbr.2026.116319},
pmid = {42259394},
issn = {1872-7549},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss driven by oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Ferroptosis, an iron-dependent and lipid peroxidation-associated form of regulated cell death, has recently been identified as a key contributor to neuronal vulnerability. Emerging evidence demonstrates that purified natural monomer compounds derived from medicinal plants exert potent neuroprotective effects by targeting ferroptosis and neuroinflammatory pathways. Representative agents such as curcumin, baicalin, resveratrol, and ginsenoside Rg1 activate nuclear factor E2-related factor-2 and glutathione peroxidase 4 signaling to preserve redox balance, while suppressing microglia-mediated inflammation through inhibition of toll-like receptor 4 pathways. This review highlights the interplay between ferroptosis and neuroinflammation in NDDs, summarizes the regulatory effects of bioactive herbal monomer compounds, and discusses recent advances in multi-omics profiling, nano-delivery strategies, and translational research. By modulating the ferroptosis-neuroinflammation axis, these compounds may represent promising therapeutic candidates for NDDs.},
}

@article {pmid42259474,
year = {2026},
author = {Ma, Z and Yang, Z and Xiao, Z and Huang, B and Wang, X},
title = {Unveiling the Multi-Target Mechanisms of Zuo Gui Wan in Alzheimer's Disease: An Integrated Study Combining Network Pharmacology, Mendelian Randomization, and Molecular Docking.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111972},
doi = {10.1016/j.brainresbull.2026.111972},
pmid = {42259474},
issn = {1873-2747},
abstract = {PURPOSE: Zuo Gui Wan (ZGW), a traditional Chinese medicine formula, shows neuroprotective potential, but the mechanisms underlying its therapeutic effects on Alzheimer's disease (AD) remain unclear. This study aims to identify the active components, molecular targets, and biological pathways of ZGW in AD using an integrated systems pharmacology approach combining network analysis and causal inference.

METHODS: Active ZGW ingredients and targets were sourced from TCMSP and BATMAN-TCM. Summary-data-based Mendelian Randomization (SMR) and colocalization analyses integrated eQTL and AD GWAS data to identify gene-AD associations. Network pharmacology, GO/KEGG enrichment, PPI analysis, and molecular docking were conducted. Selected targets were examined by CCK-8 assay and Western blot in an Aβ25-35-induced SH-SY5Y neuronal injury model treated with ZGW-containing rat serum.

RESULTS: We identified 134 bioactive ZGW compounds targeting 391 AD-related genes. SMR prioritized six targets (ACE, SRC, STAT1, LEP, EGFR, and MAPK3) associated with neuroinflammatory and cardiovascular pathways. Molecular docking suggested strong interactions between key compounds and targets, notably berberine with SRC (-10.53kcal/mol) and compound 1 (PubChem CID: 137704703) with MAPK3 (-17.22kcal/mol). In the Aβ-induced neuronal model, ZGW-containing serum partially restored cell viability, reduced ERK1/2 and STAT1 phosphorylation, and increased ACE expression.

CONCLUSION: Integrated computational analyses prioritized six potential AD-related targets of ZGW, including ACE, SRC, STAT1, LEP, EGFR, and MAPK3. Preliminary cellular experiments further supported the involvement of MAPK3/ERK and STAT1 signaling, with increased ACE expression observed after ZGW treatment. These findings provide mechanistic insight into the potential therapeutic effects of ZGW in AD.},
}

@article {pmid42259543,
year = {2026},
author = {Nelson, MB and Crecelius, C and Jones, AP and Coffey, C and Dasgupta, A},
title = {Correlation of CSF Biomarkers with Cognitive Screening Tests and PET Scan: A Tandem Approach.},
journal = {Annals of clinical and laboratory science},
volume = {56},
number = {2},
pages = {139-143},
pmid = {42259543},
issn = {1550-8080},
abstract = {OBJECTIVE: Testing for amyloid beta protein (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau at position 181: p-Tau 181) in CSF using Roche Elecsys assays has been approved by the FDA as biomarkers for Alzheimer's disease. We studied correlation between pTau181/Aβ42 ratios (>0.023 positive cutoff), screening for cognitive functions (commonly used for screening patients suspected of dementia and AD) with actual AD diagnosis based on PET scans in 143 patients.

METHODS: All Roche Elecsys (electrochemiluminescence) assays for biomarkers were run on Cobas e 801 analyzer. Imaging studies were performed using fluorodeoxyglucose PET scans. Screening patients for cognitive functions (SCFs) included either MOCA, SLUMS, STMS, or MMSE.

RESULTS: Out of 143 patients with CSF AD biomarker ratios studied, 80 patients showed positive values (mean: 0.0555), while 63 patients showed negative ratios (mean: 0.0138). We also compared biomarker results with PET imaging in 40 patients (PET scan results were not available for all patients). Chi-square analysis showed a statistically significant association between positive CSF biomarker tests and PET scans {X[2](1, N=40)=14.593; p<0.01}.
In contrast, we observed poor correlation between SCFs and PET scan results using chi-square analysis {X[2](1, N=40)=3.558, p=0.059}.
However, binary logistic regression demonstrated a combination of abnormal SCF and a positive CSF screen significantly predicted a positive imaging result {X[2](2, N=40)=15.940, p<.001}.


CONCLUSIONS: CSF pTau181/Aβ42 ratios correlated significantly better with PET scan findings compared to various SCFs. Furthermore, a combination approach that included SCF and CSF biomarkers provided better correlation with positive PET imaging.},
}

@article {pmid42259598,
year = {2026},
author = {Xu, L and Jiang, Q and Jin, Y and Lin, T and Cao, R and Xu, HD and Liu, X and Yang, Z and Zhan, W and Liang, G},
title = {A [19]F MRI/NIR-FL Nanoprobe for "Turn-On" Imaging of β-Secretase (BACE1) Activity in Alzheimer's Disease.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {},
number = {},
pages = {e1325073},
doi = {10.1002/anie.1325073},
pmid = {42259598},
issn = {1521-3773},
support = {2023YFF0724100//National Key Research and Development Program of China/ ; 22504126//National Natural Science Foundation of China/ ; 22234002//National Natural Science Foundation of China/ ; BK20250927//Natural Science Foundation of Jiangsu Province/ ; BK20232007//Natural Science Foundation of Jiangsu Province/ ; JSSCTD202409//Jiangsu Shuang Chuang Team/ ; 2025M771069//China Postdoctoral Science Foundation/ ; //Zhishan Young Scholar Program of Southeast University/ ; },
abstract = {Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder with very few therapeutic methods; thus, its early detection is urgently important. β-secretase (BACE1) is a well-recognized biomarker of early-stage AD, but its in vivo imaging-based diagnostic method is rarely reported. Herein, we report a BACE1-disassemblable nanoprobe, [19]F-Cy5.5-NP for "Turn-On" [19]F magnetic resonance/near-infrared fluorescence ([19]F MR/NIR-FL) imaging of the enzyme activity in AD in vivo. The "Turn-On" [19]F MRI signals are employed for imaging BACE1 activity with high specificity, while the "Turn-On" NIR-FL signals are used for double checking the enzyme activity with high spatial resolution. Specifically, [19]F-Cy5.5-NP, with a silent [19]F MR/NIR-FL signal is obtained from the precursor Cys(StBu)-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe(CF3)-Lys(Cy5.5)-CBT ([19]F-Cy5.5) through a CBT-Cys click reaction. Upon BACE1 cleavage, the nanoprobe disassembles, resulting in 6.8 ± 1.3-fold and 9.5 ± 0.3-fold increases of [1] [9]F NMR and NIR-FL signals in vitro, respectively. Moreover, [19]F-Cy5.5-NP renders 4.6 ± 0.9-fold/1.5 ± 0.1-fold higher [19]F MRI/NIR-FL signal in Aβ25-35-treated PC12 cells than that in normal PC12 cells. In vivo experimental results show that this nanoprobe enables the precise imaging of BACE1 activity in AD zebrafish models. We anticipate that [19]F-Cy5.5-NP could be applied for the early diagnosis of AD in clinics in the future.},
}

@article {pmid42259955,
year = {2026},
author = {Domingo, JL},
title = {Aging in a highly polluted world: challenges and solutions to prevent Alzheimer's disease.},
journal = {Archives of toxicology},
volume = {},
number = {},
pages = {},
pmid = {42259955},
issn = {1432-0738},
abstract = {Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder globally and a leading cause of disability and death among the elderly. As populations age worldwide, the epidemiological burden of AD is expected to more than double by 2050, surpassing 150 million affected individuals. While genetic susceptibility, particularly the apolipoprotein E ε4 (APOE4) allele, modulates individual risk, most AD cases are late-onset and shaped by complex interactions between genetic background and modifiable environmental exposures. Environmental pollution has emerged as a critical and potentially preventable contributor to this burden. The 2024 Lancet Commission on Dementia Prevention, Intervention, and Care has identified 14 modifiable risk factors, with air pollution explicitly included. Drawing on evidence from human epidemiological cohorts, experimental animal models, and in vitro neuronal/glial systems, the present review aims to synthesize mechanistic evidence linking environmental pollutant classes to AD-relevant neuropathology. The review examines the growing body of evidence linking major categories of environmental pollutants (ambient particulate matter, heavy metals, pesticides, PFAS, and emerging contaminants including microplastics and nanoplastics) to AD risk and pathogenesis. Special attention is given to studies showing that the characteristic neuropathological features of AD may emerge in children and young adults chronically exposed to heavily polluted urban environments, which highlights critical concerns about when and how these changes develop throughout life. Shared mechanistic pathways through which environmental pollutants promote neurodegeneration are discussed, including neuroinflammation, oxidative stress, blood-brain barrier disruption, tau kinase dysregulation, epigenetic reprogramming, and gut-brain axis dysbiosis. The review also examines the amplifying role of biological aging on neurotoxic vulnerability and proposes a comprehensive, multi-level prevention framework addressing individual exposure reduction, clinical risk identification, and population-level policy interventions.},
}

@article {pmid42259980,
year = {2026},
author = {Basri, R and Al-Kuraishy, HM and Alruwaili, M and Al-Gareeb, AI and Albuhadily, AK and Alexiou, A and Papadakis, M and Faheem, SA and Batiha, GE},
title = {Bile acids in Alzheimer's disease: a double-edged sword in gut-liver-brain signaling and neurodegeneration.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42259980},
issn = {1432-1912},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5/GPBAR1) has emerged as a mechanistic bridge linking liver-gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood-brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid-based biomarkers and therapeutic strategies targeting FXR/TGR5 signaling may represent promising avenues for future AD intervention.},
}

@article {pmid42260160,
year = {2026},
author = {El-Ghazawi, K and Aberra, YT and Veeramasu, Y and Fares, WA and Isakson, BE and Sontheimer, H and Eyo, UB and Peirce, SM},
title = {Transcriptional analyses identify pericyte-centered signaling programs altered by sex and brain region in Alzheimer's Disease.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10446-y},
pmid = {42260160},
issn = {2399-3642},
abstract = {Pericytes are critical components of the neurovascular unit (NVU), regulating endothelial cell stability, blood-brain barrier (BBB) integrity, and neuroimmune signaling. Their role in Alzheimer's Disease (AD), particularly regarding sex differences and brain region specificity, remains poorly defined. Using single-nucleus RNA sequencing analysis and cell-cell communication tools (LIANA, Tensor-cell2cell), we characterize pericyte transcriptional and signaling changes across the middle temporal gyrus (MTG) and dorsolateral prefrontal cortex (DLPFC) of AD and non-AD donors stratified by sex. We identify a pericyte-endothelial TGFβ signaling program upregulated in female AD donors specifically in the MTG, and a downregulated estrogen pathway involving pericyte-astrocyte ligand-receptor interactions, supported by increased pericyte-astrocyte separation in spatial transcriptomics. We also identify a microglia-to-pericyte program enriched for hypoxia and p53 pathways that is elevated in both sexes with regional specificity. Our findings implicate pericyte-driven communication as a mechanistic contributor to female-biased AD vulnerability, and support sex- and region-aware approaches in neurodegeneration research.},
}

@article {pmid42260188,
year = {2026},
author = {Aldaghi, M and Khatir, AA and Sepidarkish, M and Arjmandi, D and Mousavi, F and Aghapour, S and Bayani, M and Rostami, A},
title = {Association between Toxoplasma gondii seropositivity and Alzheimer's disease: a case-control study.},
journal = {Parasitology research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00436-026-08711-4},
pmid = {42260188},
issn = {1432-1955},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by declining cognitive function and memory deterioration. Emerging evidence suggests that infectious agents, including Toxoplasma gondii, may contribute to the risk of developing this disorder. Because previous studies on this association have produced limited and inconsistent results, we examined the link between T. gondii infection and Alzheimer's disease. This case-control study included 90 recently diagnosed AD patients from Ayatollah Rouhani Hospital and Clinic in Babol, Iran, and 91 healthy individuals as controls. After obtaining written informed consent, serum samples were collected from both groups. AD was determined through expert clinical evaluation, and the Mini-Mental State Examination (MMSE) was used to assess cognitive status and disease severity. Anti-T. gondii IgG antibodies were detected using ELISA. Data were analyzed in SPSS using chi-square tests, and odds ratios with 95% confidence intervals were calculated. The seroprevalence of T. gondii was 77.7% in cases and 89.0% in healthy controls. T. gondii seropositivity showed a significant inverse association with AD in both univariate analysis (OR: 0.43, 95% CI: 0.18-0.98; P = 0.04) and multivariate analysis (OR: 0.35, 95% CI: 0.14-0.92; P = 0.03). Additionally, T. gondii seropositivity was significantly associated with lower odds of greater AD severity in multivariate analysis (OR: 0.44, 95% CI: 0.20-0.97; P = 0.04). Our findings suggest an inverse association between T. gondii seropositivity and AD. Moreover, seropositivity was associated with lower odds of more severe disease. Further research is warranted to clarify the biological basis and clinical significance of this association.},
}

@article {pmid42260217,
year = {2026},
author = {Kodi, T and Nandakumar, K and Kishore, A},
title = {AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42260217},
issn = {1559-1182},
abstract = {The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing protein-3 (NLRP3) inflammasome plays a central role in inflammatory diseases, including cardiovascular, gastrointestinal, neurodegenerative, autoimmune, hepatic, renal, and pulmonary disorders. Although various cellular pathways tightly regulate its activation, the precise mechanisms remain unclear. Emerging evidence highlights adenosine monophosphate-activated protein kinase (AMPK) as a critical regulator of energy balance and cellular metabolism, suggesting its potential involvement in modulating NLRP3 inflammasome activity. This review explores the structural dynamics of the NLRP3 inflammasome and the activation of AMPK signaling. It focuses on the mechanistic pathways underlying AMPK-mediated suppression of the NLRP3 inflammasome, including autophagy-dependent regulation, sirtuin-mediated regulation, ER stress/TXNIP signaling pathway, regulation of mitochondrial homeostasis, NF-κB/MyD88-mediated priming, and maintenance of lysosomal integrity. Furthermore, the review discusses the interplay of these pathways in CNS-specific disease models, such as Ischemic stroke/cerebral ischemia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, diabetic neuropathy, and neuroinflammation models, as well as traumatic brain injury, streptozotocin-induced neuroinflammation, and lipopolysaccharide-induced neuroinflammation. Additionally, this review examined therapeutic strategies targeting the AMPK-NLRP3 axis in neuroinflammatory and neurodegenerative disorders.},
}

@article {pmid42260290,
year = {2026},
author = {Monteverdi, A and Ramusino, MC and Conca, F and Manzon, S and Redolfi, A and Lupi, E and De Grazia, M and Lorenzi, RM and Gaviraghi, M and Mazzocchi, L and Farina, LM and Costa, A and Pichiecchio, A and Cappa, SF and Wheeler-Kingshott, CAMG and Palesi, F and D'Angelo, E},
title = {Alterations in topological and dynamical parameters correlate with disease biomarkers and neuropsychological scores in prodromic stages of dementia.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-56387-8},
pmid = {42260290},
issn = {2045-2322},
abstract = {Mild cognitive impairment (MCI) is a clinical condition at the very beginning of dementia continuum whose heterogeneity prevents a precise prediction of clinical evolution. In this work, in a cohort composed of MCI, healthy controls (HC), and Alzheimer's disease (AD) patients, graph theory (GT) was combined with virtual brain modelling (TVB) to extract the information on network topology and dynamics embedded in magnetic resonance imaging data. With this approach, the analysis was extended to a multiparametric space and brought from the group to the subject-specific level. The comparison of network properties in HC, MCI, and AD revealed a profound reshaping of brain connectivity, which mainly affected the default mode, limbic, attention, and somatosensory networks. Interestingly, positivity to AD biomarkers (Aβ and τ) in MCI correlated with network topology, while a TVB parameter (i.e., recurrent excitation) correlated with reduced global cognition (MMSE score). The combination of GT and TVB parameters was superior to the individual techniques alone in providing a subject-specific phenotype of MCI sensitive to molecular biomarkers and correlated (R[2] ~ 70%) with neuropsychological scores. This, in turn, could form the basis for a more precise stratification in prodromic dementia leading, in future, to a personalized prediction of evolution and therapeutic intervention.},
}

@article {pmid42260548,
year = {2026},
author = {Canal, C and Aguilar, K and Comes, G and Sanz, E and Giralt, M and Sanchis, P and Hidalgo, J},
title = {Chronic central-targeted Interleukin-6 overexpression promotes hippocampal and cortical neuropathology in the Tg2576 mouse model of Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02101-9},
pmid = {42260548},
issn = {1758-9193},
support = {PID2021-126602OB-I00//Ministerio de Ciencia e Innovación y Fondo Europeo de Desarrollo Regional/ ; SAF2014-56546-R//Ministerio de Economía y Competitividad y Fondo Europeo de Desarrollo Regional/ ; RTI2018-101105-B-I00//Ministerio de Ciencia, Innovación y Universidades y Fondo Europeo de Desarrollo Regional/ ; },
abstract = {BACKGROUND: Interleukin-6 (IL-6) is a cytokine detected in the brains and peripheral fluids of both Alzheimer's disease (AD) patients and mouse models, where its levels correlate with amyloid-beta (Aβ) burden and plaque deposition. Interestingly, IL-6 deficiency ameliorates cognitive deficits and attenuates hippocampal neuroinflammation, whereas astrocyte-targeted IL-6 signaling via its soluble receptor accentuates pathological features in AD mouse models. These findings suggest that central IL-6 overexpression may actively drive disease manifestations. However, because IL-6 can also signal through its classical membrane-bound receptor pathway, the overall impact of central IL-6 on AD pathophysiology is still not fully elucidated.

MAIN TEXT: To explore the contribution of central IL-6 overexpression in modulating AD-related mortality, metabolic, behavioral and neuroinflammatory changes in the hippocampus and cortex, we crossed a transgenic mouse model (Tg2576) of Aβ-driven amyloidosis with mice expressing IL-6 under the Glial Fibrillary Acidic Protein promoter (GFAP-IL6), which predominantly targets astrocytes. Chronic IL-6 overexpression reduced inguinal white adiposity in both males and females and decreased body weight in females. Early behavioral alterations were observed in Tg2576 mice, with central-targeted IL-6 overexpression regulating behavior in an age- and sex-dependent manner. Increased cortical and hippocampal Aβ42/Aβ40 ratios, along with gliosis, were observed in aged female and male Tg2576 mice. Interestingly, chronic central-targeted IL-6 overexpression increased cortical and hippocampal Aβ42/Aβ40 ratios while inducing a differential distribution and/or reactivity of astrocytes and microglia in aged Tg2576 mice. In particular, central-targeted IL-6 overexpression resulted in increased overall gliosis in the cortical and hippocampal parenchyma but reduced gliosis in the vicinity of cortical and hippocampal amyloid plaques. Finally, cortical transcriptomic profiling in Tg2576 mice revealed widespread changes in immune, synaptic, and stress response pathways in response to chronic IL-6 overexpression, with cortical neuroinflammatory and neurotransmission-associated gene networks showing sex-dependent differences.

CONCLUSIONS: Our findings emphasize that chronic central-targeted IL-6 overexpression shapes the cortical and hippocampal molecular landscape underlying amyloidosis in both male and female Tg2576 mice. Thereby, we propose IL-6 as a potential target for future AD therapeutic strategies.},
}

@article {pmid42260566,
year = {2026},
author = {Ullah, F and Du, S and Jin, W and Nagar, YA},
title = {Disintegrating ipseity: a gerontological exegesis of Alzheimer's disease and relational identity in Alice Munro's fiction.},
journal = {Philosophy, ethics, and humanities in medicine : PEHM},
volume = {21},
number = {1},
pages = {},
pmid = {42260566},
issn = {1747-5341},
abstract = {BACKGROUND: Alzheimer's is a progressive disorder of the brain that gradually affects memory, personality, behaviour, identity, and interpersonal relationships, particularly among older adults. Alice Munro's novella "The Bear Came Over the Mountain" offers a compelling literary framework for exploring these impacts through narrative gerontology, a lens that emphasizes storytelling's role in shaping identity and relational bonds during ageing and illness.

METHOD: This study applies narrative gerontology to analyze Munro's depiction of Alzheimer's, focusing on the experiences of Fiona and Grant. Through detailed textual analysis, it examines the gerontological concept of "we-narrative" (shared relational identity) to understand how identity, memory loss, and relational dynamics evolve.

RESULTS: Munro portrays Alzheimer's as both a medical condition and a social experience, fragmenting Fiona's sense of self and reshaping the couple's shared identity. Fiona's fading memories unravel her narrative, diminishing her autonomy, while Grant's shift from husband to caregiver redefines their relationship. The novella's disjointed structure reflects the cognitive chaos of Alzheimer's, deepening its emotional impact. The gerontological "we-narrative," representing shared relational identity, reveals the enduring strength of their bond, as Grant's selfless actions highlight a transformed expression of love.

DISCUSSION: Dementia narrative features how caregivers' identity gradually forms through the lived experience of supporting a loved one with cognitive decline. These findings align with narrative gerontology's view that stories help individuals and caregivers navigate identity and loss. Munro's work challenges stereotypes about ageing, emphasizing the emotional complexity of caregiving and the resilience of human connections.

CONCLUSION: Munro's novella powerfully illustrates Alzheimer's multifaceted effects, using narrative to explore identity, care, and relational adaptation in the context of ageing and illness.},
}

@article {pmid42260606,
year = {2026},
author = {Ferreira Dos Santos, L and Cozachenco, D and Lima-Filho, RAS},
title = {Corticothalamic circuit and executive dysfunction in Alzheimer's disease and related tauopathies.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP291604},
pmid = {42260606},
issn = {1469-7793},
support = {3300382483424060//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; E-26/200.054/2024//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/200.203/2024//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; },
}

@article {pmid42260770,
year = {2026},
author = {Dushyant, and Nayak, S and Panchal, V and Narwal, S and Singh, J and Dhingra, AK and Sakshi, and Kaur, J and Yadav, N and Saini, J},
title = {Formulation, Development, and In vitro Evaluation of Sustained Release Buccal Films for Optimized Memantine Therapy.},
journal = {Drug metabolism and bioanalysis},
volume = {},
number = {},
pages = {},
doi = {10.2174/0131173853466482260428064458},
pmid = {42260770},
issn = {3117-3861},
abstract = {INTRODUCTION: Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is employed in moderate to severe Alzheimer's disease but has the disadvantage of low oral bioavailability owing to first-pass metabolism and multiple doses. Buccal drug delivery is one such alternative that has received attention for enhancing systemic availability and patient compliance.

METHODS: Sustained-release buccal films of memantine hydrochloride were prepared by the solvent casting technique using Hydroxypropyl Methylcellulose (HPMC) and Carbopol 940 as film-forming and mucoadhesive polymers, polyethylene glycol 400 as plasticizer, and menthol as permeation enhancer. UV and FTIR were used for preformulation studies and for compatibility testing. The films were assessed for their physicochemical properties, tensile strength, swelling studies, surface pH, drug content, residence time, and in vitro release. Optimization of the result was carried out by statistical regression analysis with Design Expert® software.

RESULTS: The prepared films possessed uniform thickness, good mechanical properties, surface pH compatible with the buccal mucosa, and provided constant drug release for 8 h. FTIR studies revealed that there was no chemical incompatibility between memantine and excipients. F11 was found to have the highest drug content (90.1%), a good swelling index (19.4%), good folding endurance, and a conducive residence time of approximately 5 h.

DISCUSSION: The sustained release and the positive mucoadhesive properties observed are in line with those reported for other buccal film systems. The swelling profile and drug release kinetics were markedly affected by the polymer concentration.

CONCLUSION: The developed sustained-release buccal films of memantine hydrochloride demonstrated favorable physicochemical and in vitro release characteristics, indicating their potential as a noninvasive alternative drug delivery system. Although buccal administration is theoretically capable of bypassing hepatic first-pass metabolism and improving systemic availability, such benefits could not be conclusively established in the absence of in vivo pharmacokinetic and ex vivo permeation studies. Therefore, further investigations are required to validate these potential advantages.},
}

@article {pmid42260778,
year = {2026},
author = {Singh, H and Singh, BK and Kumar, A and Chauhan, K and Chauhan, B and Kumar, A and Mishra, AK and Chopra, S and Agarwal, V and Chopra, H and Greig, NH},
title = {Exploring the Cellular and Molecular Mechanisms Underlying Alzheimer's Disease Utilizing Cerebral Organoids Derived from Patient-specific Induced Pluripotent Stem Cells (iPSCs): A Review with Implications for Surgical Interventions.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X428563260430050900},
pmid = {42260778},
issn = {1875-6190},
abstract = {Alzheimer's disease (AD) remains a major unmet medical need characterized by progressive cognitive decline and multifactorial pathology. Induced pluripotent stem cell (iPSC) technology provides an invaluable platform to model patient-specific and late-onset disease mechanisms. Advances in reprogramming strategies and neuronal differentiation protocols have improved the fidelity of human-derived neuronal models by preserving age-related and epigenetic features relevant to AD. Cortical organoids generated from iPSCs have further enabled the reconstruction of three-dimensional brain-like structures, facilitating the study of amyloid and tau pathology, synaptic dysfunction, and neuroinflammatory interactions in a physiologically relevant context. Ongoing innovations, such as microglial integration, vascularization, and induction of cellular aging, continue to enhance the translational accuracy of these models. iPSC and organoid systems are increasingly used for mechanistic dissection of AD-related pathways, genotype-phenotype correlations, and high-throughput therapeutic screening. Nevertheless, challenges related to reproducibility, maturation, and scalability remain barriers to clinical translation. The review also highlights ethical, regulatory, and societal considerations inherent to human stem cell-based disease modeling. Together, these developments underscore the transformative potential of iPSC-derived models in advancing mechanistic understanding and therapeutic discovery for Alzheimer's disease.},
}

@article {pmid42260779,
year = {2026},
author = {Kong, W and Su, P and Xu, Y and Wang, S and Wei, K and Ke, F and Wen, G and Yu, Y},
title = {Multitask Sparse Canonical Correlation Analysis and Regression with Parameter Decomposition based on Deep Subspace Reconstruction for Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050449671260513065443},
pmid = {42260779},
issn = {1875-5828},
abstract = {INTRODUCTION: Multimodal imaging genomics overcomes the limitations of singlemodality analyses, offering a more comprehensive understanding of brain pathophysiology. Traditional methods like sparse canonical correlation analysis (SCCA) and its improved versions have been widely used to identify key brain regions and single nucleotide polymorphisms (SNPs) associated with neurodegenerative diseases, such as Alzheimer's disease (AD). However, the fusion of complex and heterogeneous multimodal neuroimages, along with the linear formulation of these methods, limits their ability to capture complex, nonlinear relationships in imaging-genetics data.

METHODS: To address this limitation, a novel framework, DSR-PDMTSCCAR, is introduced for multimodal AD data. This framework combines deep subspace reconstruction for nonlinear mapping and parameter decomposition to extract modality-consistent and modality-specific features across structural MRI (sMRI) and positron emission tomography (PET) data. Additionally, multitask sparse canonical correlation analysis (MTSCCA) is incorporated to capture correlations across multiple tasks, facilitating modeling of heterogeneous multimodal associations.

RESULTS: Evaluations on simulated datasets and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort show that DSR-PDMTSCCAR outperforms conventional methods, including SCCA, partial least squares (PLS), and deep canonical correlation analysis (DCCA). The method identifies biomarkers such as hippocampal and amygdalar alterations in sMRI/PET and APOErelated genetic variants, all consistent with AD pathology.

DISCUSSION: The maximum canonical correlation coefficient (CCC) achieved was 0.1759, compared to 0.1525 for MTSCCA. The PET-SNP correlation (0.1896) was more than double that of MTSCCA (0.0864).

CONCLUSION: The DSR-PDMTSCCAR framework offers robust performance in multimodal imaging- genetics analysis, providing enhanced insights into AD pathophysiology and advancing precision medicine.},
}

@article {pmid42260810,
year = {2026},
author = {Cong, L and Ji, H and Yang, H and Kuang, G and Liu, H and Sun, H and Liu, Y},
title = {Causal effects of mental disorders on stroke subtypes: A proteome-wide Mendelian randomization and mediation analysis.},
journal = {Medicine},
volume = {105},
number = {23},
pages = {e49108},
doi = {10.1097/MD.0000000000049108},
pmid = {42260810},
issn = {1536-5964},
abstract = {Observational studies have demonstrated associations between mental disorders and stroke, yet causal relationships and potential molecular mechanisms remain elusive. To clarify this, we performed a bidirectional 2-sample Mendelian randomization (MR) analysis using genome-wide association studies summary statistics to assess the causal effects of 7 major mental disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit/hyperactivity disorder [ADHD], Alzheimer disease, and Parkinson disease) on stroke subtypes. Analyses were divided into discovery and validation cohorts of European ancestry, followed by MRlap and meta-analysis to obtain pooled estimates. To explore potential circulating protein mediators, 4907 plasma cis-protein quantitative trait loci (cis-pQTLs) from deCODE Genetics were screened, followed by Bayesian co-localization and 2-step MR mediation analyses. Our findings revealed that ADHD was consistently associated with an increased risk of any stroke (AS), any ischemic stroke (AIS), and particularly large-artery atherosclerotic stroke (LAS; odds ratio = 1.455; 95% confidence interval: 1.077-1.967). Mediators screening showed genetic liability to ADHD was linked to elevated circulating matrix metallopeptidase-12 (MMP12; β = 0.141, P = .005), which conferred protection against AIS and LAS, potentially lowering LAS risk by 7.5%. In conclusion, this MR study suggests ADHD is a causal risk factor for ischemic stroke, especially LAS. Paradoxically, circulating MMP12 acts as a protective mediator, modestly reducing this risk by 7.5%. These findings require validation in future experimental and cohort studies.},
}

@article {pmid42261077,
year = {2026},
author = {Fakorede, S and Cheng, K and Huang, CK and Martin, LE and Akinwuntan, AE and Burns, JM and Devos, H},
title = {The Effect of Postural Control on Attentional Resource Allocation in Alzheimer's Disease: An Event-Related Potential Study.},
journal = {Perceptual and motor skills},
volume = {},
number = {},
pages = {315125261459181},
doi = {10.1177/00315125261459181},
pmid = {42261077},
issn = {1558-688X},
abstract = {ObjectiveTo examine how the postural demand of quiet standing, compared to sitting, affects the allocation of attentional resources during a concurrent cognitive task in healthy older adults and individuals with Alzheimer's disease (AD).Methods87 healthy older adults (age 71.7 ± 4.2 years; MoCA 28.9 ± 1.1) and 16 individuals with AD (age 74.3 ± 5.1 years; MoCA 19.6 ± 6.3) completed a two-minute auditory novelty oddball task (50 stimuli: 80% frequent, 10% rare, 10% novelty) in both standing and sitting positions. Neural activity was recorded using electroencephalography (EEG). We used linear mixed models to compare P3 event-related potentials (ERPs) across groups and conditions, focusing on the P3b component (conscious stimulus evaluation) and the P3a component (automatic novelty detection). Behavioral outcomes were accuracy and reaction times on the oddball task, and sway velocity collected from a head-mounted accelerometer.ResultsA significant condition × group interaction was found for P3b latency in response to frequent stimuli (p = 0.003). While sitting, the AD group showed shorter P3b latencies than healthy older adults (p = 0.036). However, this pattern reversed under postural load: individuals with AD had significantly longer P3b latencies when standing compared to sitting (p = 0.01), whereas healthy older adults showed the opposite pattern, with significantly decreased latencies (p = 0.04). No significant effects were found for P3b amplitude or for the P3a component. Postural condition did not significantly impact behavioral outcomes in either group.ConclusionsQuiet standing may impose a selective neural cost on individuals with AD, reflected in slower conscious cognitive processing, while appearing to act as an arousing factor that facilitates faster processing in healthy older adults. Maintaining posture might require a reallocation of limited attentional resources that disrupts higher-order processing in AD.},
}

@article {pmid42261236,
year = {2026},
author = {Malvankar, A and Raut, M and Singh, SK and Singh, R and Mahindroo, N and Bajad, N},
title = {A comprehensive exploration of the structure-activity relationships, multitarget strategies, and therapeutic mechanisms of triazole scaffolds in Alzheimer's disease.},
journal = {Future medicinal chemistry},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17568919.2026.2684615},
pmid = {42261236},
issn = {1756-8927},
abstract = {The deposition of the Aβ peptide extracellularly as diffused and neuritic plaques and intracellular hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles (NFTs) are the key pathological changes observed in the progression of AD. Despite advances in the neuroscience research, the discovery and development of effective therapeutic agents have become challenging task for AD. The molecules modulating multiple targets involved in the disease attracted much attention as promising tools for the effective therapeutic efficacy. Triazole scaffold has been consistently rewarded as a promising versatile lead molecule with a pivotal position in modern medicinal chemistry. It has shown potent inhibitory activity against different targets involved in the progression of the AD including activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid beta (Aβ) accumulation, tau aggregation, neuroinflammation and oxidative stress. Recent reviews label 1,2,3-triazole as first choice scaffold for designing multifunctional hybrid molecules for AD. A comprehensive literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases covering publications from 2000 to 2026. This review critically analyzes the evolution of triazole-based therapeutics from single-target cholinesterase inhibitors to modern multitarget-directed ligands. We systematically evaluate how the structural versatility of the 1,2,3- and 1,2,4-triazole cores facilitates interactions with key AD pathological hallmarks.},
}

@article {pmid42261248,
year = {2026},
author = {Choi, JS and Hur, JY},
title = {The Innate Immune Protein IFITM3 as a γ-Secretase Modulatory Protein: From Inflammation to Alzheimer's Disease.},
journal = {DNA and cell biology},
volume = {},
number = {},
pages = {10445498261456523},
doi = {10.1177/10445498261456523},
pmid = {42261248},
issn = {1557-7430},
abstract = {The mechanisms of Alzheimer's disease (AD) development are complex, and the detailed roles of neuroinflammation in AD still need to be elucidated. With various genetic and environmental risk factors, the accumulation of harmful amyloid plaques containing amyloid-β (Aβ) peptides is one of the main hallmarks of AD. Recent findings show that the innate immune protein interferon-induced transmembrane protein 3 (IFITM3) binds to γ-secretase and modulates Aβ production, providing a direct link between neuroinflammation, amyloidogenesis, and the pathogenesis of AD. In this review, we explore IFITM3-mediated modulation of γ-secretase complex activity and its pivotal role in AD pathology during neuroinflammation. Furthermore, we also provide an overview of the recent growing evidence connecting the roles of infection, the immune system, and AD pathogenesis.},
}

@article {pmid42261516,
year = {2026},
author = {Yoshida, Y and Tanito, M},
title = {Cognitive Assessment in Glaucoma Care: A Narrative Review of Clinical Rationale, Screening Tools, and Implementation Challenges.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e108458},
pmid = {42261516},
issn = {2168-8184},
abstract = {In recent years, increasing attention has been directed toward the association between glaucoma and cognitive impairment, with a growing number of reports highlighting their interrelationship. With the progression of population aging, the coexistence of these two conditions is expected to rise further. Cognitive impairment may influence glaucoma management in multiple ways, including difficulties in performing subjective examinations such as visual field testing, reduced adherence to topical medications, and an elevated risk of postoperative complications. Consequently, integrating cognitive assessment into glaucoma care may be particularly relevant in selected patient populations, such as older adults or those with suspected adherence or reliability issues. This narrative review aims to summarize the current evidence on the relationship between glaucoma and cognitive impairment and to provide an overview of commonly used cognitive screening tools. In addition, we discuss the clinical implications of cognitive dysfunction in glaucoma management and highlight emerging digital approaches for cognitive assessment. Given that much of the available evidence is observational and that glaucoma-specific validation of cognitive screening strategies remains limited, this review provides insights into optimizing glaucoma care in an aging society and outlines directions for future research.},
}

@article {pmid42261679,
year = {2026},
author = {Zauszniewski, JA and Burant, CJ and Almutairi, RR and Meyer, K and Irani, E},
title = {Use of Personal and Social Resourcefulness by Adult-Child and Spousal Caregivers of Persons with Dementia.},
journal = {International journal of aging & human development},
volume = {},
number = {},
pages = {914150261456742},
doi = {10.1177/00914150261456742},
pmid = {42261679},
issn = {1541-3535},
abstract = {PurposeThis study examined the use of personal and social resourcefulness when experiencing anger, anxiety, sadness, decision-making, and financial distress among adult-child and spousal caregivers of persons with dementia.MethodsBaseline data on 10 Resourcefulness Scale[©] items measuring personal and social resourcefulness in response to anger, anxiety, sadness, decision-making, and financial distress were obtained from 127 adult-child and 112 spousal caregivers of persons with dementia.ResultsAdult-child and spousal caregivers similarly used personal resourcefulness for financial distress (62%-68%) and both personal and social resourcefulness when angry (67%), sad (87%-92%), and making decisions (77%-98%). Spousal caregivers used both personal and social resourcefulness when anxious (37%), while adult-child caregivers used only personal resourcefulness (46%). The findings were similar across age, race, and gender subgroups.ConclusionsFuture research should explore the effects of other situational factors (e.g., caregiving burden) on resourcefulness. Gerontological healthcare professionals should assess the caregiver-care recipient relationship when determining and tailoring interventions.},
}

@article {pmid42252078,
year = {2026},
author = {Huang, Y and Xie, X and Huang, Z and Gangal, H and Chen, R and Wang, X and Li, J and Wang, J},
title = {Chronic Alcohol Exposure Produces Pathology-Dependent Corticostriatal Circuit Remodeling in Aβ- and Tau-Based Mouse Models of Alzheimer's Disease.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {111069},
doi = {10.1016/j.neuropharm.2026.111069},
pmid = {42252078},
issn = {1873-7064},
abstract = {Chronic alcohol consumption is a major risk factor for Alzheimer's disease (AD), yet how alcohol exposure alters neural circuits under distinct pathological conditions remains poorly understood. Here, we used a humanized Aβ knock-in model (hAPP-KI) and a tauopathy model (PS19) to test how the same alcohol exposure affects distinct pathological contexts. In hAPP-KI mice, alcohol exposure increased cortical Aβ burden, enhanced excitatory synaptic transmission in the medial prefrontal cortex (mPFC), and reduced glutamatergic transmission from the mPFC to the dorsomedial striatum (DMS). In contrast, in PS19 mice, alcohol exposure increased tau phosphorylation and elevated mPFC-to-DMS glutamatergic transmission without altering local cortical excitatory input. Alcohol exposure was also associated with distinct microglial responses across pathological contexts. To assess microglial contributions to cortical excitatory regulation, we depleted microglia in wild-type mice and observed enhanced cortical glutamatergic transmission. Together, these findings suggest pathology-dependent circuit remodeling and microglial responses associated with alcohol exposure in AD models.},
}

@article {pmid42252207,
year = {2026},
author = {Ince, S and Van Hulle, C and Kollmorgen, G and Quijano-Rubio, C and Gleason, C and Bendlin, BB and Okonkwo, O and Asthana, S and Blennow, K and Zetterberg, H and Johnson, SC and Love, S and Miners, JS},
title = {Dysregulated TIE-2 expression is associated with blood-brain barrier leakiness and Alzheimer's disease-related neuropathology.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70109},
doi = {10.1111/bpa.70109},
pmid = {42252207},
issn = {1750-3639},
support = {ARUK-SRF-2019A-001//Alzheimer's Research UK/ ; NIH R01AG027161//NIH National Center for Advancing Translational Sciences (NCATS)/ ; P50AG033514//NIH National Center for Advancing Translational Sciences (NCATS)/ ; R01AG054059//NIH National Center for Advancing Translational Sciences (NCATS)/ ; R01 AG062167/AG/NIA NIH HHS/United States ; UF1AG051216//NIH National Center for Advancing Translational Sciences (NCATS)/ ; UL1TR000427//NIH National Center for Advancing Translational Sciences (NCATS)/ ; //Ministry of National Education in Türkiye/ ; },
abstract = {Cerebral hypoperfusion and blood-brain barrier (BBB) leakiness are related to cognitive decline and the onset and spread of Aβ and tau pathology in Alzheimer's disease (AD). Disrupted angiopoietin/TIE (ANGPT/TIE) signalling causes neurovascular instability and BBB leakiness accelerating cognitive decline and disease pathology in mouse models of AD. To explore ANGPT/TIE signalling in human AD, we measured CSF TIE-1 and TIE-2 levels by ELISA in two independent clinical dementia cohorts, and serum and CSF Tie-1/-2 in paired CSF and serum samples from neurologically normal individuals. ANGPT1, ANGPT2, TIE-1 and TIE-2 levels were measured by ELISA in crude homogenate (CH) and microvessel-enriched fractions (MVFs) of post-mortem human parietal cortex in relation to biochemical markers of cerebral perfusion (MAG:PLP1) and BBB leakiness (parenchymal fibrinogen) in a control, AD, and vascular dementia (VaD) cohort. CSF soluble TIE-2 was elevated in AD biomarker+ve individuals and correlated positively with CSF t-tau and p-tau, and markers of BBB leakiness, neuronal injury, and neuroinflammation. Tissue TIE-2 levels were significantly reduced in Braak tangle stage (BS) III-IV, that is, brains with early-intermediate AD pathology, and were lower in MVFs in end-stage AD pathology (BSV-VI) than in controls or VaD. Lower levels of MVF TIE-2 correlated with markers of cerebral hypoperfusion and BBB leakiness. Our study reveals a reciprocal relationship between elevated CSF and reduced tissue TIE-2 expression that is related to markers of tau pathology, BBB leakiness, and cerebral hypoperfusion, providing novel insights into ANGPT/TIE signalling in AD.},
}

@article {pmid42252271,
year = {2026},
author = {Zeng, C and Wang, B and Bao, Y},
title = {Hippocampal inflammasome enrichment in intermediate Alzheimer's disease: Strong spatial findings, but clearer stage and mechanistic definition are needed.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70103},
doi = {10.1111/bpa.70103},
pmid = {42252271},
issn = {1750-3639},
support = {GZY-KJS-ZJ-2025-099//TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform/ ; },
}

@article {pmid42252273,
year = {2026},
author = {Li, D and Liu, X and Lu, Y and Yu, G},
title = {[Protective effect of Cuscuta chinensis Lam. against Aβ1-42-induced oxidative injury in HT22 cells and its mechanism].},
journal = {Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences},
volume = {},
number = {},
pages = {1-10},
doi = {10.3724/zdxbyxb-2025-0418},
pmid = {42252273},
issn = {1008-9292},
abstract = {OBJECTIVES: To investigate the protective effect of Cuscuta chinensis Lam. against oxidative injury in an Alzheimer's disease (AD) cell model and its molecular mechanism.

METHODS: Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze and identify the chemical components of Cuscuta chinensis Lam.. An oxidative injury model was established in HT22 neuronal cells induced by Aβ1-42. Cell viability was measured by CCK-8 assay, and apoptosis was detected by Annexin V-FITC/PI double staining. Intracellular reactive oxygen species (ROS) levels were detected using the DCFH-DA probe, and the expression of antioxidant- and apoptosis-related proteins was examined by Western blotting.

RESULTS: A total of 381 chemical components were identified from Cuscuta chinensis Lam., among which astragalin, hyperoside, kaempferol, and quercetin were the main constituents. Cell experi-ments showed that Cuscuta chinensis Lam. at concentrations of 0.50, 0.75, and 1.00 mg/mL increased the viability of Aβ1-42‑treated HT22 cells, decreased the apoptosis rate, reduced ROS production, upregulated the expression of the antioxidant-related proteins heme oxygenase-1 and NQO1, downregulated the expression of the apoptosis-related protein cytochrome C, and reduced the ratios of activated caspase-3/caspase-3 and Bax/Bcl-2.

CONCLUSIONS: Cuscuta chinensis Lam. may attenuate oxidative injury in AD model cells by activating the endogenous antioxidant defense system and inhibiting the mitochondrial-dependent apoptotic pathway.},
}

@article {pmid42252274,
year = {2026},
author = {Yu, Z and Wang, Y and Li, Y and Shen, F and Wang, Y},
title = {[Research progress on vascular endothelial growth factor C in meningeal lymphatic vessel-mediated clearance of amyloid β-protein].},
journal = {Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences},
volume = {},
number = {},
pages = {1-8},
doi = {10.3724/zdxbyxb-2025-0549},
pmid = {42252274},
issn = {1008-9292},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein (Aβ) as a core pathological feature. Meningeal lymphatic vessels are crucial for Aβ clearance, and their dysfunction accelerates AD progression. Vascular endothelial growth factor C (VEGF-C), through activation of vascular endothelial growth factor receptor 3 and downstream pathways, synergistically promotes lymphangiogenesis, enhances lymphatic permeability, and regulates lymphatic fluid flow, thereby improving Aβ clearance efficiency. Genetic factors and aging-related declines in VEGF-C further impair meningeal lymphatic function, creating a vicious cycle. Although VEGF-C intervention has shown cognitive benefits in AD models, clinical translation faces challenges including non-specific activation of signaling pathways and interindividual variability. Future research should focus on precise regulation of VEGF-C and development of individualized AD therapeutic strategies targeting meningeal lymphatic vessels. This review summarizes the molecular mechanisms, influencing factors, and intervention strategies of VEGF-C in regulating meningeal lymphatic vessel function to promote Aβ clearance, aiming to provide insights for AD prevention and treatment.},
}

@article {pmid42252276,
year = {2026},
author = {de Rivero Vaccari, JP and Davis, DA and Sawaya, AP and Garamszegi, SP and Sun, X and Barreda, A and Bramlett, HM and Gultekin, SH and Dietrich, WD and Keane, RW and Vontell, RT},
title = {Comments to the "Letter to the Editor" for the manuscript titled "Increased expression of inflammasome signaling genes and proteins in selective brain regions in the intermediate stage of Alzheimer's disease".},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70113},
doi = {10.1111/bpa.70113},
pmid = {42252276},
issn = {1750-3639},
support = {//University of Miami and the State of Florida, Department of Health (COHFA) awarded to W. Dalton Dietrich, COHFA/ ; },
abstract = {Beta amyloid diffuse plaques, neurofibrillary tangles and neuritic plaques, are increased in densities at the intermediate stage of Alzheimer's neuropathological change. These pathological changes releasing Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs). These molecules are sensed by pattern recognition receptors (PRRs) and trigger intracellular responses. One response is the activation of the inflammasome sensors NLRP1, NLRP3, and AIM2 to oligomerize with ASC speck to form the inflammasome complex and initiate the downstream signaling of GSDMD mediated pyroptosis. Another response is the increase in genes to manufacture proinflammatory cytokines, the inflammasome formation activates the cleavage of the proinflammatory cytokines to the activated forms, which are secreted into the extracellular environment and recruit a widespread inflammation.},
}

@article {pmid42252335,
year = {2026},
author = {Behl, T and Jayabalan, K and Ballal, S and Sahoo, S and Jayasingh Chellammal, HS and Gulati, M and Anand, K and Jha, SK and Gasmi, A},
title = {A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42252335},
issn = {1559-1182},
mesh = {Humans ; *Blood-Brain Barrier/pathology/physiopathology/metabolism ; *Aging/pathology ; Animals ; *Neurodegenerative Diseases/pathology/physiopathology ; },
abstract = {The pathophysiology of neurodegenerative illnesses is increasingly understood to be influenced by vascular aging, with blood-brain barrier (BBB) disruption emerging as a crucial mechanistic connection. Comprising endothelial cells, pericytes, astrocytes, and microglia, the BBB is a complex neurovascular unit (NVU) that strictly regulates molecular trafficking and shields neural tissue from circulating toxins and immune cells, therefore maintaining central nervous system homeostasis. The integrity of the BBB is compromised as people age due to structural and functional changes in the cerebrovasculature, such as endothelial senescence, pericyte loss, mitochondrial dysfunction, and persistent low-grade inflammation. These alterations speed up neuronal damage and encourage the development of classical proteinopathies like tau aggregation and amyloid-β by making it easier for neurotoxic proteins, immunological mediators, and metabolic waste to enter the brain parenchyma. BBB disruption is both an early occurrence and a factor in the development of neurodegenerative diseases including Alzheimer's disease, cerebral amyloid angiopathy, and vascular dementia. It exacerbates neuroinflammation, hinders clearance processes, and contributes to cognitive decline. Recent developments in single-cell omics, fluid biomarkers, and molecular imaging have made it possible to identify and characterize BBB failure in preclinical and clinical contexts, creating new opportunities for early diagnosis and treatment. Restoring BBB function and addressing vascular aging are two viable approaches to alter the course of neurodegenerative illnesses and enhance their prognoses. The processes, effects, and translational potential of vascular aging and BBB degradation in neurodegeneration are summarized in this review, which also identifies new treatment targets and research objectives for the future.},
}

Humans
*Blood-Brain Barrier/pathology/physiopathology/metabolism
*Aging/pathology
Animals
*Neurodegenerative Diseases/pathology/physiopathology

@article {pmid42252466,
year = {2026},
author = {Chai, L and Zhan, Y and Huang, Y and Tian, M and Zhao, G and Ni, J and Xiong, X and Huang, J and Lin, B},
title = {Plasma p-tau as a biomarker for the differential diagnosis of Alzheimer's disease: a systematic review and meta-analysis.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02104-6},
pmid = {42252466},
issn = {1758-9193},
support = {2023J01876//Natural Science Foundation of Fujian Province/ ; },
abstract = {BACKGROUND: With the clinical implementation of amyloid-targeting therapies, accurately differentiating Alzheimer's disease (AD) from other neurodegenerative dementias is imperative. This systematic review and meta-analysis synthesized data on the diagnostic performance of three plasma phosphorylated tau (p-tau) isoforms identified through a comprehensive literature search, namely p-tau181, p-tau217, and p-tau231.

METHODS: We searched major databases up to November 30, 2025, for studies comparing blood p-tau levels in AD versus biologically confirmed non-AD neurodegenerative disorders. Data were synthesized using bivariate random-effects models to calculate pooled sensitivity, specificity, area under the curve (AUC), and diagnostic odds ratio (DOR).

RESULTS: Thirty-three studies comprising 6,138 participants were included. Blood p-tau biomarkers demonstrated robust overall accuracy (AUC 0.90) and a high positive likelihood ratio (PLR 3.77). Comparison of isoforms revealed that plasma p-tau217 exhibited superior performance (AUC 0.95; Sensitivity 0.93) with a remarkable DOR of 57.98, which was nearly six-fold higher than that of p-tau231 (DOR 9.83). Subgroup analyses showed exceptional specificity for differentiating AD from behavioral variant frontotemporal dementia (bvFTD) (0.91) and vascular dementia (0.83), but discriminative ability against dementia with Lewy bodies (DLB) was significantly lower (Specificity 0.69; DOR 7.54). Furthermore, plasma-based assays (AUC 0.92, 95% CI 0.88-0.96) significantly outperformed serum-based methods (AUC 0.76, 95% CI 0.74-0.78), as evidenced by non-overlapping confidence intervals.

CONCLUSIONS: Plasma p-tau217 is the superior biomarker for the differential diagnosis of AD, particularly for ruling out FTD, though distinguishing AD from DLB remains challenging due to mixed pathology. The distinct superiority of plasma over serum supports the exclusive use of plasma-based protocols for clinical implementation.},
}

@article {pmid42252493,
year = {2026},
author = {Dittrich, A and Arslan, B and Skillbäck, T and Rydén, L and Kvartsberg, H and Gobom, J and Blennow, K and Zetterberg, H and Kern, S and Skoog, I},
title = {Prevalence of high-risk plasma p-tau217 levels and 5-year transition of risk status in 70-year-olds.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71545},
doi = {10.1002/alz.71545},
pmid = {42252493},
issn = {1552-5279},
support = {//European Partnership on Metrology/ ; 2023-00356,2022-01018,2019-02397,2019-02075,2019-02075_15//the Swedish Research Council/ ; 2012-5041,2015-02830,2013-8717,2017-00639,2019-01096,2022-00882//the Swedish Research Council/ ; 101053962//European Union's Horizon Europe research and innovation programme/ ; ALFGBG-984092//the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement/ ; ALFGBG-71320//the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement/ ; #201809-2016862//Alzheimer Drug Discovery Foundation (ADDF)/ ; //the AD Strategic Fund/ ; (#ADSF-21-831376-C,#ADSF-21-831381-C,#ADSF-21-831377-C,and#ADSF-24-1284328-C/ALZ/Alzheimer's Association/United States ; //European Union's Horizon Europe Research and Innovation Programme/ ; #22HLT07//NEuroBioStand/ ; //the Bluefield Project/ ; //Cure Alzheimer's Fund/ ; //the Erling-Persson Family Foundation/ ; //Familjen Rönströms Stiftelse/ ; //Familjen Beiglers Stiftelse/ ; //Stiftelsen för Gamla Tjänarinnor/ ; #FO2022-0270//Hjärnfonden/ ; 860197//European Union's Horizon 2020 research and innovation programme/ ; //the National Institute for Health and Care Research University College London/ ; //Hospitals Biomedical Research Centre/ ; UKDRI-1003//the UK Dementia Research Institute at UCL/ ; //anonymous donor/ ; //Swedish state under the agreement between the Swedish government and the county councils/ ; ALFGBG-1005471 ALFGBG-965923 ALFGBG-81392 ALF GBG-771071//the ALF-agreement/ ; AF-842471,AF-737641,AF-929959,AF-939825,FO2024-0341-HK-76//Alzheimerfonden/ ; AF-554461AF-647651AF-743701AF-844671AF-930868AF-940139AF-968441AF-980935//Alzheimerfonden/ ; //Stiftelsen Psykiatriska Forskningsfonden/ ; FO2024-0097,FO2014-0207FO2016-0214FO2018-0214FO2019-0163FO2020-0235//The Swedish Brain Foundation/ ; ALFGBG-984092//the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement/ ; ALFGBG-71320//the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement/ ; ALFGBG-984092//the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement/ ; ALF965812 ALF 716681//the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement/ ; //Swedish Research Council for Health/ ; 2013-1202 2018-00471//Working Life and Wellfare/ ; 2013-2300 2013-2496 2018-00471//Working Life and Wellfare/ ; //Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse/ ; //Eivind och Elsa K:son Sylvans stiftelse/ ; AGECAP2013-2300//Forskningsrådet om Hälsa, Arbetsliv och Välfärd/ ; 2013-2496//Forskningsrådet om Hälsa, Arbetsliv och Välfärd/ ; 2018-00471//Forskningsrådet om Hälsa, Arbetsliv och Välfärd/ ; //National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, the UK Dementia Research Institute at UCL/ ; JPND2021-00694//EU Joint Programme - Neurodegenerative Disease Research/ ; //European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant/ ; //Familjen Erling-Perssons Stiftelse/ ; //Olav Thon Stiftelsen/ ; #201809-2016862//Alzheimer's Drug Discovery Foundation/ ; //Swedish State Support for Clinical Research/ ; },
abstract = {INTRODUCTION: High-risk plasma p-tau217 levels predict amyloid-β pathology in Alzheimer's disease, but little is known about the prevalence and temporal dynamics in the general population.

METHODS: Participants from the Gothenburg H70 Birth Cohort Study in Sweden were examined (n = 1157) and re-examined after 5-7 years (n = 771). Prevalence and 5-7 year transition of high-risk plasma p-tau217 status was determined among community-dwelling 70-year-olds.

RESULTS: High-risk plasma p-tau217 prevalence was 3.6% at age 70 and 7.0% at age 75-77 years. Eighty-nine percent remained low-risk and 4% converted to high-risk at follow-up. Prevalence of dementia at follow-up was 1.7% if remaining in the low-risk group and 21.4% if transitioning to the high-risk group. Prevalence of dementia among participants staying in the high-risk group was 16.7% at follow-up.

DISCUSSION: Individuals with low-risk plasma p-tau217 were unlikely to transition over 5-7 years. However, transitioning to a higher risk-category was associated with a higher prevalence of cognitive disability.},
}

@article {pmid42252507,
year = {2026},
author = {Cary, GA and Keegan, S and Wiley, JC and Gockley, J and Butler, RR and Longo, FM and Levey, AI and Greenwood, AK and Leal, K and Carter, GW and , },
title = {Mapping cross-domain drivers of Alzheimer's disease risk through integrated network analysis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71564},
doi = {10.1002/alz.71564},
pmid = {42252507},
issn = {1552-5279},
support = {U54 AG065187/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disorder with numerous known risk factors. Identification of which genetic factors are causal drivers is difficult due to the long disease prodrome in an inaccessible organ. The application of integrative, systems-level approaches are crucial for addressing this complexity.

METHODS: Sixteen biological domain specific interaction networks were derived from the top AD risk-enriched proteins within each domain. Weighted key driver analysis (wKDA) identified influential hub nodes within each network.

RESULTS: Distinct processes and drivers were identified within each domain's network. Domains including structural stabilization, endolysosome, and lipid metabolism were especially influential. Integrating key drivers across domains identified consistent drivers such as CTNNB1, ACSL1, and ALDH3A2, suggesting fundamental roles contributing to AD risk.

DISCUSSION: This highly integrative network-based approach identified context-dependent drivers and enabled the inference of interactions between domains. The identified drivers suggest potential targets for future therapeutic development.},
}

@article {pmid42252508,
year = {2026},
author = {Dewenter, A and Bürger, K and Janowitz, D and Paulus, M and Nuscher, B and Hirsch, F and Gesierich, B and Steward, A and Frontzkowski, L and Roemer-Cassiano, SN and Zhu, Z and Biel, D and Klonowski, M and Biechele, G and Stoecklein, S and Ewers, M and Duering, M and Tiedt, S and Brendel, M and Franzmeier, N and , },
title = {Differential associations of plasma biomarkers with Alzheimer's disease and small vessel disease: A multimodal imaging study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71530},
doi = {10.1002/alz.71530},
pmid = {42252508},
issn = {1552-5279},
support = {1175//Legerlotz Stiftung/ ; 1032//Legerlotz Stiftung/ ; },
abstract = {INTRODUCTION: We investigated how plasma biomarkers (phosphorylated tau 217 [ptau217], glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) relate to imaging markers of small vessel disease (SVD) and Alzheimer's disease (AD), and cognition in memory clinic patients.

METHODS: 76 memory clinic patients underwent plasma biomarker assessment, neuropsychological testing, and 3T MRI. SVD burden was assessed using white matter hyperintensity (WMH) volume, mean skeletonized mean diffusivity (MSMD), and fiber density. AD-related neurodegeneration was captured by AD-signature cortical thickness and fiber-bundle cross-section. Findings were validated in 41 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with amyloid-/tau-positron emission tomography (PET).

RESULTS: Associations varied between biomarkers. NfL showed strongest associations with SVD burden, ptau217 with AD-related neurodegeneration, while GFAP was linked to both. SVD markers were associated with processing speed, whereas AD markers were most associated with memory.

DISCUSSION: NfL relates to SVD burden, while ptau217 remains most sensitive to AD-related biomarkers. GFAP's dual associations suggest overlapping biological processes. Together, coexisting SVD should be considered when interpreting plasma biomarkers in memory clinic patients.},
}

@article {pmid42252510,
year = {2026},
author = {Constantino, NJ and Irmen, RE and Lanning, MJ and Turner, SM and Ashley, CC and Carroll, CM and Neary, EM and Rubinow, D and Snipes, JA and Macauley, SL},
title = {Early microglial response to amyloid plaques drives sleep loss in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71579},
doi = {10.1002/alz.71579},
pmid = {42252510},
issn = {1552-5279},
support = {R01AG068330//BrightFocus Foundation/ ; R01AG093847//BrightFocus Foundation/ ; A20201775S//BrightFocus Foundation/ ; P30AG072946//Coins for Alzheimer's Research Trust/ ; T32NS115704//Cure Alzheimer's Fund/ ; //Institutional Development Award/ ; //NIGMS/ ; P30GM127211/GF/NIH HHS/United States ; P20GM148326//NIH Center of Biomedical Research Excellence (COBRE) in CNS Metabolism/ ; },
abstract = {INTRODUCTION: Sleep disruption is an early feature of Alzheimer's disease (AD), but the cellular mechanisms linking amyloid pathology to sleep loss remain unclear.

METHODS: Electroencephalography/electromyography (EEG/EMG) recordings, quantitative EEG analysis, and sleep deprivation were performed in APPswe/PSEN1dE9 (APP/PS1) mice at different stages of pathology relative to normal aging. Amyloid burden and microglial density were quantified with whole-brain light-sheet microscopy. CSF1R-mediated microglial depletion explored effects of microglia on sleep loss.

RESULTS: Amyloid plaques caused non-rapid eye movement (NREM) sleep loss that did not worsen with increased plaque burden. Aging reduced REM sleep and eliminated sleep rebound. Amyloid pathology was associated with cortical hyperexcitability, network desynchrony, and microglial expansion extending beyond plaque-bearing regions into thalamocortical and white matter networks governing sleep-wake dynamics. Microglial depletion restored > 2 hours of sleep per day without altering amyloid burden.

DISCUSSION: Microglia are a causal, reversible driver of amyloid-associated sleep loss, positioning sleep and EEG-based metrics as sensitive biomarkers of presymptomatic AD.},
}

@article {pmid42252511,
year = {2026},
author = {Chen, K and Pineau, E and Koletar, M and Trevisiol, A and He, JS and Hill, M and Goubran, M and Sled, J and McLaurin, J and Stefanovic, B},
title = {Stable neuronal representations underlie cognitive resilience to Alzheimer's disease pathology.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71570},
doi = {10.1002/alz.71570},
pmid = {42252511},
issn = {1552-5279},
support = {//the Canadian Consortium on Neurodegeneration in Aging/ ; CIHR PJT191806/CAPMC/CIHR/Canada ; NIH R01AG084681/NH/NIH HHS/United States ; },
mesh = {Animals ; *Alzheimer Disease/pathology/physiopathology ; *Neurons/physiology/pathology ; Rats ; Disease Models, Animal ; Male ; *Cognition/physiology ; Rats, Inbred F344 ; Maze Learning/physiology ; Hippocampus/pathology/physiopathology ; },
abstract = {INTRODUCTION: While Alzheimer's disease (AD) typically elicits progressive cognitive decline, some individuals with significant AD pathology maintain cognition. Understanding the neuronal underpinnings of such cognitive resilience would propel the development of interventions for delaying dementia.

METHODS: We used Barnes Maze testing to identify cognitively resilient 13-month-old TgF344-AD rats (established AD) and their non-transgenic littermates, followed by Neuropixels recording from 8500 neurons during repeated somatosensory stimulation, and culminating in post mortem tau and amyloid load quantifications.

RESULTS: Cognitively resilient TgF344-AD rats recruited fewer neurons and displayed more stable neuronal representations during repeated stimulations in cortical excitatory and hippocampal inhibitory ensembles, with reduced excitatory spike burstiness and a distinct pattern of functional synaptic connectivity. These associations existed independently of amyloid levels.

DISCUSSION: For the first time, our study revealed neuronal population-level hallmarks of maintained cognition that may serve as a novel neurophysiological biomarker of cognitive resilience and a target for stabilizing cognition.},
}

Animals
*Alzheimer Disease/pathology/physiopathology
*Neurons/physiology/pathology
Rats
Disease Models, Animal
Male
*Cognition/physiology
Rats, Inbred F344
Maze Learning/physiology
Hippocampus/pathology/physiopathology

@article {pmid42252512,
year = {2026},
author = {Jarvis, I and Besser, L and Finlay, J and Hystad, P and Lane, KJ and Hunter, RF and James, P and Jiménez, MP and Nieuwenhuijsen, M and van den Bosch, M and Van Riper, D and Lee, J and Doiron, D and Brook, J and Adar, SD and Brauer, M},
title = {Urban greenspace and dementia: Measures, mechanisms, and methodological guidance.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {6},
pages = {e71557},
doi = {10.1002/alz.71557},
pmid = {42252512},
issn = {1552-5279},
support = {U24AG088894/AG/NIA NIH HHS/United States ; RT-2024-03917//Michael Smith Health Research BC/ ; 194052/CAPMC/CIHR/Canada ; },
mesh = {Humans ; *Dementia/epidemiology/prevention & control ; *Parks, Recreational ; Alzheimer Disease ; *Urban Population ; },
abstract = {Urban greenspace has been associated with improved cognition and reduced Alzheimer's disease (AD) and AD-related dementias (ADRD) risk, but findings remain mixed, study quality varies, and evidence is largely cross-sectional. To advance the field, we offer guidance to select and apply greenspace exposure measures in AD/ADRD research. Our interdisciplinary expert working group synthesized existing knowledge and developed consensus-based recommendations through collaborative discussion. In this paper, we outline hypothesized pathways, summarize data sources and measurement approaches, and propose criteria and recommendations to select and apply greenspace exposure measures in research. Based on hypothesized pathways, we recommend tree canopy cover for stress reduction, attention restoration, and improved mental health; parks for increased physical and social activity; and greenness for reduced harmful exposures, highlighting the Normalized Difference Vegetation Index as capturing multiple pathways. We also identify future research priorities to advance understanding of greenspace-AD/ADRD associations and support more rigorous, comparable, and policy-relevant evidence.},
}

Humans
*Dementia/epidemiology/prevention & control
*Parks, Recreational
Alzheimer Disease
*Urban Population

@article {pmid42252551,
year = {2026},
author = {Chiatto, LM and Buccarello, L and Carota, G and Calabrò, RS and Rifici, C and Esposito, E and Ardizzone, A and Caruso, G},
title = {The Use of Statins in Parkinson's and Alzheimer's Disease: A 2021-2025 State-of-the-Art Review of Clinical and Preclinical Evidence.},
journal = {Pharmacology research & perspectives},
volume = {14},
number = {3},
pages = {e70280},
doi = {10.1002/prp2.70280},
pmid = {42252551},
issn = {2052-1707},
abstract = {Statins, widely prescribed for cardiovascular prevention, have emerged as potential disease-modifying agents in neurodegenerative disorders due to their pleiotropic effects on cholesterol metabolism, neuroinflammation, oxidative stress, and protein aggregation. Over the past decade, growing interest has focused on the potential repurposing of statins for Parkinson's disease (PD) and Alzheimer's disease (AD); however, clinical evidence remains heterogeneous and, in some cases, contradictory. This state-of-the-art review synthesizes clinical and preclinical studies published between 2021 and 2025 to critically evaluate the therapeutic potential and limitations of statins in PD and AD. Recent observational studies and large-scale cohort analyses suggest that long-term statin use may be associated with a reduced risk of incident PD and AD, as well as slower cognitive decline in selected patients' subgroups. However, these associations appear to depend on factors such as statin lipophilicity, treatment duration, and genetic background. Preclinical models provide mechanistic support, showing that statins can attenuate neuroinflammation, modulate microglial activation, reduce α-synuclein aggregation in PD models, and interfere with amyloid-β production and tau phosphorylation in AD models. Nevertheless, randomized controlled trials remain limited in number and often underpowered, and some reports indicate neutral or even adverse neurological outcomes, underscoring the complexity of cholesterol-dependent and cholesterol-independent mechanisms in the central nervous system (CNS). Collectively, the evidence from 2021 to 2025 highlights both the therapeutic promise and the unresolved challenges of statin repurposing in neurodegenerative diseases. Future research should prioritize well-designed clinical trials and biomarker-driven patient stratification to determine whether statins can be effectively leveraged as adjunctive disease-modifying therapies in PD and AD.},
}

@article {pmid42252587,
year = {2026},
author = {Jin, H},
title = {PET Molecular Probes for Neuroinflammation in Neurodegenerative Diseases: Progress and Prospects.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00338},
pmid = {42252587},
issn = {1948-7193},
abstract = {Neuroinflammation is a central pathological process underlying neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis. Positron emission tomography (PET) molecular probes now enable the noninvasive, quantitative visualization of neuroinflammatory processes in the living brain. This review surveys recent advances in PET probes targeting microglial activation markers─including the 18 kDa translocator protein (TSPO), the purinergic P2X7 receptor (P2X7R), colony-stimulating factor 1 receptor (CSF1R), and sphingosine-1-phosphate receptor 1 (S1PR1)─as well as astrocyte reactivity markers such as monoamine oxidase B (MAO-B) and imidazoline-2 binding sites (I2BS). I discuss the evolution from first-generation TSPO ligands to polymorphism-insensitive third-generation tracers, highlight emerging targets beyond TSPO, and evaluate the translational value of these probes for early diagnosis, disease staging, treatment monitoring, and drug development. Current challenges-including limited cellular specificity, genetic polymorphism effects, quantification difficulties, and clinical accessibility barriers─are analyzed alongside promising solutions. Integrating neuroinflammation PET into multimodal biomarker frameworks will be essential for advancing precision medicine in neurodegenerative diseases.},
}

@article {pmid42253015,
year = {2026},
author = {Wang, Z and Pu, R and Gao, B and Cai, W and Yang, G},
title = {Oral microbiota associated with tooth loss and cognitive function in older adults: Evidence from NHANES.},
journal = {Journal of periodontology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jper.70154},
pmid = {42253015},
issn = {1943-3670},
support = {82271001//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: The aim of this study is to investigate the association between tooth loss and cognitive decline and to explore the potential role of salivary microbial genera in this relationship in a nationally representative population.

METHODS: Data from 1,413 adults aged ≥ 60 years in NHANES 2011-2012 were analyzed. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning Tests, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Salivary microbiome profiles were obtained from a subsample of 661 participants using 16S rRNA sequencing. Complex survey regression, PERMANOVA, and multivariable microbial association analyses were applied. Mediation analyses were conducted as exploratory analyses to evaluate potential microbial pathways linking tooth loss with cognitive outcomes.

RESULTS: Moderate tooth loss was associated with higher odds of low global cognition (OR = 2.91, 95%CI: 2.01-4.23), low AFT (OR = 1.57, 95%CI: 1.03-2.39), and low DSST (OR = 2.15, 95%CI: 1.47-3.16) after adjustment. Sixteen genera were associated with at least one cognitive metric, including Prevotellaceae_NA, Phocaeicola, and Lactobacillus. In exploratory mediation analyses, three organic acid-producing genera (Lactobacillus, Lachnospiraceae_NA, and Leptotrichiaceae_NA) were identified as potential contributors to the association between tooth loss and cognition.

CONCLUSION: Tooth loss was associated with cognitive decline in older adults, and both conditions were accompanied by differences in salivary microbial composition. Exploratory mediation analyses suggested that certain organic acid-producing taxa may contribute to the observed association.

PLAIN LANGUAGE SUMMARY: Tooth loss is common in older adults and has been linked to problems with memory and thinking, but the reasons for this connection are not fully understood. In this study, we used data from a large national health survey of adults aged 60 years and older to examine tooth loss, results from several cognitive tests, and the types of bacteria found in saliva. We found that older adults with more missing teeth were more likely to perform poorly on tests measuring memory, attention, and processing speed. We also observed that some types of oral bacteria were related to both tooth loss and cognitive performance. In exploratory analyses, several groups of bacteria that produce organic acids were linked to the relationship between tooth loss and cognitive outcomes. These findings suggest that differences in the oral microbial community may be one of several biological pathways connecting oral health and cognitive function. Understanding how oral health, diet, and oral bacteria interact may help researchers better understand factors related to cognitive aging and to identify potential targets for future research and prevention strategies.},
}

@article {pmid42253176,
year = {2026},
author = {Bhatt, M and Das, B},
title = {Thiolated Chitosan-Stearic Acid Thiol-Linked Biomimetic Hydrogels for Axonal Regrowth and Neuronal Tissue Regeneration.},
journal = {ACS applied bio materials},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsabm.5c02580},
pmid = {42253176},
issn = {2576-6422},
abstract = {Neuronal disorders like spinal cord injury, stroke, peripheral neuropathy, and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, etc., need regenerative approaches and therapeutics like tissue engineering and cell therapy for neuronal systems. Significant factors such as neuronal damage, impaired immune response, and glial scar formation create a hostile environment for neural repair and functional recovery. To overcome these challenges, the development of biocompatible and bioactive biomaterials is essential for therapeutic applications. In this work, a thiolated chitosan-stearic acid (Tch-Sa) hydrogel was prepared by modifying chitosan and stearic acid with free thiol (SH) groups, mimicking the high lipid content and GaGs in neuronal tissue. The hydrogel was crosslinked via disulfide linkages. The hydrogels were characterized using FTIR, [1]H NMR, Raman spectroscopy, and TGA. Rheological evaluation demonstrated stable mechanical behavior, with storage and loss moduli showing structural consistency. In vitro cytocompatibility studies with N2a neuronal cells showed good adhesion, proliferation, and gradual morphological development. By day 7, cells displayed extended axonal projections. Immunofluorescence staining revealed increased expression of neuronal proteins, supporting the hydrogel's role in promoting neuronal differentiation and maturation. Moreover, the introduction of thiol groups enhanced cell permeability, mucoadhesive properties, and axonal outgrowth, suggesting that this material may be helpful in neuronal tissue engineering applications.},
}

@article {pmid42253201,
year = {2026},
author = {Tarkowska, A and Furmaga-Jabłońska, W and Pluta, R},
title = {Long-Term Consequences of Perinatal Asphyxia in the Development of Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050432278251204130006},
pmid = {42253201},
issn = {1875-5828},
abstract = {Despite remarkable progress in medicine, perinatal asphyxia (PA) remains a significant clinical problem, and concerns regarding its long-term complications are increasingly being raised. Emerging evidence indicates that similar pathological pathways are activated following PA and during neurodegeneration in Alzheimer's disease (AD). These similarities involve various mechanisms, including alterations in AD-related proteins and their gene expression. Disturbances in neurotransmitter function can lead to excitotoxicity and cell death via necrosis and delayed apoptosis. Additionally, as observed in AD, dysregulation of autophagic processes has been reported. Pathological changes initiated by hypoxia in the newborn may trigger chronic neuroinflammation that persists long-term. Similarly, neuroinflammation plays a critical role in the pathogenesis of AD. Other common mechanisms include oxidative stress and mitochondrial dysfunction. Estrogens appear to have a protective effect in both PA and AD; however, ovaries exposed to PA may exhibit a reduced ovarian reserve, potentially diminishing neuroprotection later in life. Epigenetic modifications have also been proposed as a link between PA and AD. This review focuses on the changes that occur in the neonatal brain following PA, with particular emphasis on long-term consequences. We highlight common pathogenetic and causal pathways that may connect PA to the development of AD. Furthermore, we summarize key studies from the past 25 years addressing these topics and briefly discuss current research directions in the treatment of experimental and clinical PA.},
}

@article {pmid42253283,
year = {2026},
author = {Gonzalez, CE and Schurman, CA and Wilson, KA and Schilling, B and Ellerby, LM and Tang, SY},
title = {Viscoelastic and Morphologic Changes in the Lumbar Intervertebral Discs of the 5xFAD Mouse Model of Alzheimer's Disease.},
journal = {JOR spine},
volume = {9},
number = {2},
pages = {e70171},
pmid = {42253283},
issn = {2572-1143},
abstract = {BACKGROUND: Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD.

AIMS: The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD.

MATERIALS AND METHODS: Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we measured the lumbar IVD's extracellular matrix composition, the three-dimensional structure, histopathological degeneration, and mechanical behaviour.

RESULTS: The amount of collagen, glycosaminoglycans, and advanced glycation end-products in the IVD did not differ in the 5xFAD animals. Likewise, the 5xFAD IVDs were not histopathologically degenerated. However, the IVD volume, measured by contrast-enhanced microCT, was larger in the 5xFAD animals (p = 0.046; 1-β = 0.53; Cohen's d = 1.19). Morphologically, the 5xFAD IVD heights were homogeneous and flatter than the WT IVDs (p = 0.043; 1-β = 0.60; Cohen's d = 1.41). Finally, dynamic micro compression revealed that 5xFAD IVDs have higher loss tangent (p = 0.0062; 1-β = 0.85; Cohen's d = 1.60) and greater energy dissipation (p = 0.0379; 1-β = 0.55; Cohen's d = 1.21).

DISCUSSION: Shifts in viscoelastic behaviour and disc morphology are associated with early tissue degradation and affect the IVD's ability to efficiently recover from mechanical loading, predisposing the IVD to eventual degeneration.

CONCLUSION: This work suggests that IVD's structure, morphology, and mechanics are affected by AD. Future work will focus on defining the molecular mechanisms of these changes in the IVD and their consequences in individuals with AD.},
}

@article {pmid42253369,
year = {2026},
author = {Sadhukhan, T and Rai, N and Hipolito, MMS and Shelby, M and Mejía Mondragón, CI and Sadhukhan, S and Idowu, A and Varghese, RS and Sajid, MS and Ressom, HW and Kalejaiye, A and Obisesan, TO and Misiak-Christian, M and Nwulia, EA},
title = {Proteomic profiling of olfactory exfoliates from people with subjective cognitive complaints reveal networks of olfactory biomarkers of cognitive performance.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1781518},
pmid = {42253369},
issn = {1663-4365},
abstract = {INTRODUCTION: Partly due to the inaccessibility of olfactory brain regions vulnerable to early Alzheimer's Disease (AD) for repeated sampling, proteomic networks underlying progressive cognitive decline remain poorly understood. The olfactory mucosa (OM), an accessible part of the olfactory system, reflects central nervous system physiology and pathology, and represents a promising site for biomarker discovery. This study aimed to identify olfactory proteomic markers and pathways associated with performance in the logical memory II recognition (LM II_recog) subtest of the Wechsler Memory Scale among older adults with subjective cognitive complaints.

METHODS: Clinical, olfactory, and cognitive assessments were conducted on 108 adults aged 55-85 years from the Washington, DC region. Nasal exfoliates were sampled from the upper nasal cavities, and protein extracts from these samples were analyzed by mass spectrometry (MS). Linear regression with false discovery rate (FDR) correction (q < 0.1) was used to identify proteins associated with LM II_recog performance, and ingenuity pathway analysis (IPA) was applied to determine functional pathways.

RESULTS: A total of 137 proteins meeting the FDR q < 0.1 threshold were found to be linearly correlated with LM II_recog scores. Of the top 10 most significant proteins, six (PLOD1, MFN2, NGFR, PPP2R5E, C4A/C4B, and ITGAV) have previously been linked to AD and/or cognitive function, underscoring their potential as biomarkers of cognitive impairment. Ingenuity pathway analysis using the knowledge base machine learning (ML) platform revealed several disease pathways highly represented among the significant proteins. These included Hyperactive Behavior, Neuromuscular Disease, Tauopathy, Behavioral Deficits, Alzheimer's Disease, Progressive Dementia, Degenerative Dementia, Alzheimer's or Frontotemporal Dementia, all of which were associated with LM II_recog performance in the elderly population.

DISCUSSION: This study demonstrates the feasibility of using OM-derived proteomics to identify molecular signatures associated with cognitive performance and highlights the OM as a potential site for non-invasive biomarker discovery. These findings provide a foundation for future studies integrating OM profiling with established AD biomarkers.},
}

@article {pmid42253387,
year = {2025},
author = {Persaud, V and Wertheimer, AI},
title = {Assessing the Equitable Use of Formulary Drug Tier Systems: Consequences for Geriatric Patient Population Access and Accessible Medication.},
journal = {Innovations in pharmacy},
volume = {16},
number = {2},
pages = {},
pmid = {42253387},
issn = {2155-0417},
abstract = {Background: This study examines the implications of formulary drug tier systems on the accessibility and affordability of medications for the elderly/geriatric population within the New York metropolitan area. By systematically reviewing the Medicare insurance formularies and evaluating the most prescribed medicines with reported beneficial outcomes for ailments frequently experienced by the geriatric population, this research identifies disparities in drug tier placements and the cost of dispensing that may affect patient outcomes. The focus is on five prevalent conditions: Alzheimer's dementia, Chronic Obstructive Pulmonary Disease, Rheumatoid Arthritis, Ischemic Heart Disease, and Diabetes Mellitus Type 2 (T2DM). The findings aim to highlight the need for more equitable healthcare policies that consider the financial and medical needs of the elderly population. Methods: This study reviewed the formulary tier systems used by Medicare, the primary insurance provider for the elderly in New York City. The research focused on medications prescribed for Alzheimer's disease, COPD, rheumatoid arthritis, ischemic heart disease, and diabetes. Data on tier placements were extracted from Medicare Part D formularies, with a detailed examination of the criteria for tier assignment. The study identified the three most prescribed medications for each condition, using data from relevant health organizations and literature. An economic analysis was conducted to compare the costs associated with these medications, assessing the financial burden on patients. Results: The study revealed a prevalence of chronic conditions among New York City's elderly population. Medications commonly prescribed for these conditions were reviewed, with a focus on their placement within the Medicare Formulary Tier system and associated costs. The analysis highlighted substantial variations in cost and tier placement, affecting patient affordability and adherence. For example, Alzheimer's medications like galantamine and rivastigmine were found in higher tiers, leading to increased out-of-pocket expenses, while COPD treatments such as Symbicort and Trelegy Ellipta, although in preferred tiers, still imposed significant financial burdens. Rheumatoid arthritis drugs showed a wide cost range, with Humira in Tier 5 presenting the highest financial challenge. Similarly, ischemic heart disease and type 2 diabetes medications varied in affordability, with drugs like Eliquis and Steglatro positioned in higher tiers, significantly impacting patient costs and potential treatment adherence. Conclusion: Elderly patients in the United States, especially those dealing with chronic conditions are facing a substantial financial strain due to the increasing prices of prescription medications. Even with recent initiatives like the Inflation Reduction Act aimed at lowering expenses, the financial burden persists, causing issues with treatment adherence and negative health results. The results highlight the pressing requirement for more effective policy actions that support price transparency, promote the utilization of cost-effective generics, and deter the unwarranted classification of generic drugs in higher formulary tiers. It is crucial to handle these problems to guarantee fair access to medications for all elderly individuals, specifically those who qualify for both Medicare and Medicaid.},
}

@article {pmid42253437,
year = {2026},
author = {Harel, M and Leibovici, A and Itzhaki, N and Ravona-Springer, R and Moshier, E and Doniger, GM and Gottlieb, A and Bahat, Y and Bendlin, BB and Zeilig, G and Plotnik, M and Beeri, MS and Livny, A},
title = {Virtual reality-based cognitive-motor training in middle-aged adults at high Alzheimer's disease risk improves frontal cortex cerebral blood flow: A randomized controlled trial.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70265},
pmid = {42253437},
issn = {2352-8737},
abstract = {INTRODUCTION: Alzheimer's disease (AD) pathological processes begin decades before symptom onset. Early intervention in high-risk populations may be crucial for prevention. We investigated the effect of an intervention utilizing virtual reality (VR) cognitive-motor training on cerebral blood flow (CBF) and cognitive functioning in middle-aged adults at high AD risk due to parental history.

METHODS: In this randomized controlled trial, participants (n = 79) were randomly assigned to: VR cognitive-motor training while walking on a treadmill (VR+T, n = 24, treatment); VR cognitive training without treadmill (VR-T, n = 21, active control); treadmill walking while watching documentaries (TV+T, n = 20, active control); or no intervention (n = 14, passive control). Training consisted of 45-min sessions, twice weekly, for 12 weeks. CBF was measured at resting state using arterial spin labeling (ASL) at baseline, 3-month, and 6-month follow-up. Cognition was assessed using a comprehensive neuropsychological battery. We applied the intent-to-treat approach.

RESULTS: All groups improved in executive functions and memory over time (all p-values < 0.05), with no consistent between-group differences at follow-up. CBF of the VR+T group significantly increased at 3 months in the superior (p = 0.013, middle (p = 0.014), and inferior (p = 0.003) frontal gyri compared to the passive control group, which showed a decline in CBF over the same period. No significant differences in frontal CBF change were observed between VR+T and the TV+T active control group. This increase was sustained for 6 months in the superior (p = 0.035) and middle (p = 0.028) frontal gyri. In contrast, in the middle temporal gyrus, the VR+T group had lower CBF at 3 months, compared to the VR-T (p = 0.033) and to the passive control groups (p = 0.004).

DISCUSSION: Cognitive-motor VR training increased CBF in frontal regions susceptible to early AD-related changes in middle-aged adults at high AD risk. This intervention shows promise as a preventive approach and may be suitable for implementation as a home-based program for individuals at high risk.},
}

@article {pmid42253438,
year = {2026},
author = {Toubasi, AA and Al-Sayegh, TN},
title = {Peripheral immune markers in dementia: A systematic review and meta-analysis of risk, severity, and pathological correlates.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70270},
pmid = {42253438},
issn = {2352-8737},
abstract = {INTRODUCTION: Systemic inflammation and innate immune activation have been implicated in dementia; however, prior studies were limited by small sample sizes. We conducted this study to evaluate the association between peripheral immune markers and the future risk of mild cognitive impairment (MCI) and dementia, their ability to differentiate between dementia causes, and their correlation with disease severity and pathological biomarkers.

METHODS: On September 8, 2025, we searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible articles included cohort and case-control studies assessing the association between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), or systemic inflammatory index (SII) and the risk of developing MCI or dementia, as well as their association with disease severity and pathological biomarkers. Outcomes were the risk of MCI and dementia (Alzheimer's disease, vascular dementia, and Parkinson's disease dementia), dementia severity assessed by the Mini-Mental State Examination, and cerebrospinal fluid or pathological markers including amyloid beta (Aβ)42, Aβ40, and tau. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled as effect estimates.

RESULTS: Our analysis included 947,020 participants from 23 studies. NLR and SII, but not PLR, were associated with increased risk of dementia (NLR: HR = 1.24, 95% CI: 1.15-1.34; SII: HR = 1.08, 95% CI: 1.03-1.13) and MCI (NLR: HR = 2.78, 95% CI: 1.57-4.90; SII: HR = 1.28, 95% CI: 1.04-1.56). No differential associations were observed across dementia causes. NLR and SII were correlated with worse dementia (NLR: r = -0.22, p = 0.033; SII: r = -0.17, p = 0.041) and MCI severity (NLR: r = -0.30, p = 0.010; SII: r = -0.23, p = 0.025). NLR, but not SII, was associated with Aβ42, Aβ40, and tau.

DISCUSSION: NLR and SII may provide valuable insights when advanced biomarker testing is limited by technological or financial barriers.},
}

@article {pmid42253439,
year = {2026},
author = {Nguyen, TT and Chakalov, BT and Van Noord, M and DeCarli, C and Hoch, JS},
title = {Worth their weight in gray matter? A narrative review of cost-effectiveness analyses of monoclonal antibodies for Alzheimer's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70267},
pmid = {42253439},
issn = {2352-8737},
abstract = {INTRODUCTION: Monoclonal antibodies (mAbs) for Alzheimer's disease (AD) represent major therapeutic advances, but their economic value is uncertain. This review narratively examines cost-effectiveness analyses (CEAs) of aducanumab, lecanemab, and donanemab for early-onset AD.

METHODS: We searched Medline (via PubMed) and EMBASE in April 2026 and incremental cost-effectiveness ratio (ICER) reports for CEAs of these mAbs. Inclusion required sufficient data to calculate ICERs. Two reviewers independently screened studies, and risk of bias was assessed using Risk of Bias in Systematic Reviews. Data were synthesized narratively due to methodological heterogeneity.

RESULTS: Of 755 records screened, 16 CEAs met inclusion criteria (six aducanumab, eight lecanemab, one aducanumab/donanemab, one lecanemab/donanemab). Almost all aducanumab studies reported ICERs that exceeded commonly cited US willingness‑to‑pay thresholds (e.g., $100,000-$150,000 per quality-adjusted life year [QALY]), with ratios ranging from $127,461 to $1,581,276/QALY (2026 USD). Lecanemab results were mixed, with manufacturer‑funded models reporting ICERs below commonly cited thresholds, while other models generally exceeded them. The single donanemab analysis versus standard of care reported an ICER of $214,760/QALY (2026 USD), above commonly cited thresholds, and a Brazilian analysis comparing donanemab with lecanemab reported an ICER of $1,477,604/QALY (2026 USD). No independent study found any mAb cost savings.

DISCUSSION: ICER variability across studies, despite reliance on the same clinical trials, reflects sensitivity to assumptions and potential sponsorship bias. Evidence is limited by small numbers of CEAs, reliance on modeled rather than real-world data, and absence of formal risk-of-bias scoring for individual CEAs. The cost-effectiveness of AD mAbs in the US context remains uncertain.},
}

@article {pmid42253440,
year = {2026},
author = {Hoang, MT and Zenker, AM and Saha, S and Gerdtham, UG and Trépel, D},
title = {Economic evaluations of strategies targeting pre-diagnosis dementia populations: A systematic review.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70236},
pmid = {42253440},
issn = {2352-8737},
abstract = {This review aims to appraise and summarize the best available evidence from economic evaluations (EEs) of strategies targeting populations prior to a diagnosis of dementia. A comprehensive search was conducted in EMBASE, PubMed, EconLit, Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL), and The NHS Economic Evaluation Database (NHS EED). Publications were dually screened and assessed against eligibility criteria, and reporting quality was appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) framework. Seventeen full EEs met the inclusion criteria; all were conducted in high-income countries and covered strategies in identification (29%), risk reduction (65%), and other strategies (6%). The number of publications from 2016 to 2025 tripled compared to the preceding periods. Most risk-reduction strategies were cost-effective and exhibited high reporting quality. The average reporting quality, based on the CHEERS framework, was 72%, with a noticeable improvement observed in articles published after 2020. Overall, the findings suggest that most risk-reduction strategies may offer good value for money. However, evidence remains limited, specifically in low- and middle-income countries; therefore, additional EEs are needed to guide future investment in strategies targeting pre-diagnosis dementia populations.},
}

@article {pmid42253441,
year = {2026},
author = {Othman, M and Khedr, E and Heikal, S and Yousef, MH and Fawi, G and El Farrash, S and Salama, S and Abdelshafi, M and Elsheikh, NG and Tawfik, HM and Hassanin, HI and Haridy, NA and Ahmed, GK and Elftoh, NA and Ibrahim, A and Qayaty, A and Ali, EM and Atputhavadivel, A and Shamma, S and Yousri, NA and Rizig, M and Salama, M},
title = {APOE-associated disease risk and sex-specific effects in Egyptian Alzheimer's disease: an exploratory study.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70268},
pmid = {42253441},
issn = {2352-8737},
abstract = {INTRODUCTION: The apolipoprotein E (APOE) gene is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), particularly the ε4 allele. Evidence suggests that women carrying at least one APOE ε4 allele have a higher risk of developing AD compared to men. However, data addressing genetic risk and sex-specific effects in Middle Eastern and North African populations remain limited.

METHODS: To address this gap, we evaluated APOE allele frequencies, their association with AD risk, and their contribution to sex-specific variability in a cohort of 63 clinically diagnosed AD patients and 201 cognitively healthy controls recruited across Egypt.

RESULTS: The APOE ε3 allele was the most prevalent in both AD cases (83.3%) and controls (83.6%). The ε4 allele was more frequent among AD patients (12.7%) than controls (8.0%) (adjusted odds ratio [OR] = 1.09, 95% confidence interval [CI]: 0.46 to 2.49, p = 0.85), while the ε2 allele was less frequent in AD patients (4.0%) compared to controls (8.5%) (adjusted OR = 0.82, 95% CI: 0.24 to 2.36, p = 0.73). However, neither association reached statistical significance after Benjamini-Hochberg false discovery rate correction. Sex-stratified analyses revealed no significant sex-specific effects of APOE alleles.

CONCLUSION: This pilot study provides the first characterization of APOE genotype and allele frequencies in Egyptians with clinically confirmed AD. No statistically significant association was observed between APOE status and AD risk in either males or females. Larger, geographically representative studies are needed to further elucidate the role of APOE in AD susceptibility within the Egyptian population and to explore potential alternative genetic or environmental contributors.},
}

@article {pmid42253443,
year = {2026},
author = {Zhou, X and Zhang, G and Hu, Q and Shao, H and Yang, T and Wang, J and Liang, X and Zhao, Q and Ding, D},
title = {Association of Excessive Daytime Sleepiness With Long-Term Incident Dementia: The Role of β-Amyloid and White Matter Injury.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70272},
pmid = {42253443},
issn = {2352-8737},
abstract = {INTRODUCTION: Excessive daytime sleepiness (EDS) is common in community-dwelling older adults, but its association with long-term incident dementia remains unclear. The roles of Alzheimer's disease (AD) pathology and vascular-related white matter injury in this association were merely studied.

METHODS: We included 617 dementia-free participants from the Shanghai Aging Study with up to 10 years of follow-up. At baseline, EDS was assessed with the Epworth Sleepiness Scale (ESS) and plasma phosphorylated tau (p-tau)217 was measured using a single-molecule immune-array assay. Cognitive decline was evaluated using the Mini-Mental State Examination (MMSE), and incident dementia was determined by expert consensus during follow-up. A magnetic resonance imaging marker of white matter injury (peak width of skeletonized mean diffusivity [PSMD]) was derived from diffusion tensor imaging, and gray matter volume was assessed from T1-weighted imaging in a subcohort.

RESULTS: At baseline, 66 participants (10.7%) had EDS and showed lower MMSE scores. EDS was associated with a higher risk of incident dementia (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.09-3.92), especially among individuals with low p-tau217 (HR 4.94, 95% CI 1.75-13.93) independent of sleep disturbance after adjusting for age, sex, and education. Higher ESS was related to AD pathology-dependent patterns of brain atrophy and to higher PSMD. PSMD modified the associations between EDS and cognitive decline, and incident dementia. Participants with both high PSMD and EDS showed the highest dementia risk.

DISCUSSION: EDS may help identify older adults with low AD biomarker burden who are at increased risk of dementia, independent of nocturnal sleep disturbance. White matter injury may contribute to this risk, supporting a vascular vulnerability pathway.},
}

@article {pmid42253499,
year = {2026},
author = {Thakore, R and Aldén, M and Gustavsson, N and Danielson, L and Lins, L and Sánchez, JD and Arensburg, AR and Paulus, A and da Silva, IAN and Skoryk, V and Kayed, R and Gouras, GK and Deierborg, T and Heuer, A and Konings, SC and Klementieva, O},
title = {Early Amyloid Formation and Neuroinflammatory Response in a Bigenic Mouse Model Expressing Human α-Synuclein and Aβ.},
journal = {Parkinson's disease},
volume = {2026},
number = {},
pages = {7303965},
pmid = {42253499},
issn = {2090-8083},
abstract = {Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies. A common feature of these disorders is the misfolding and aggregation of α-synuclein (α-syn) and amyloid-β (Aβ) proteins into amyloid structures, which disrupt cellular homoeostasis and drive disease progression. While Aβ typically forms extracellular deposits and α-syn accumulates in intracellular inclusions, both ultimately contribute to neuronal damage and neurodegeneration. Increasing in vitro evidence suggests that these proteins can interact, altering their structural properties and, in turn, their biological effects; however, the consequences of their co-occurrence in vivo remain unclear. To address this gap, we examined whether α-syn modulates Aβ deposition and associated neuroinflammation at early stages using a physiologically relevant bigenic mouse model coexpressing human α-syn and APP knock-in Aβ. Using combined histological and biochemical analysis, we characterised Aβ load and microglial responses at early time points. Our results indicate that α-syn expression is associated with altered early Aβ deposition and microglial morphology in vivo. Specifically, while early Aβ deposits were detected in both Aβ/α-syn and Aβ-control mice from 2 months of age, at 4 and 6 months, reduced number and size of Aβ microdeposits was observed in the Aβ/α-syn model. The reduction in Aβ load was accompanied by a more ramified microglial morphology consistent with a less activated microglial state. Whether this delayed response reflects protection or impaired immune surveillance remains unclear. Our findings highlight the complexity of indirect Aβ and α-syn interactions and the need for further studies to clarify their functional impact. The newly generated bigenic mice provide a relevant platform to investigate early co-pathology and its role in disease progression.},
}

@article {pmid42253513,
year = {2026},
author = {Neelamegam, M and Patil, S and Griner, S and Nhpang, R and Hwang, J and Yeh, YS and Kline, N},
title = {Exploring Dementia Awareness, Beliefs, and Attitudes among Asian Indian Immigrants in the United States.},
journal = {Ethnicity & disease},
volume = {36},
number = {1},
pages = {15-21},
pmid = {42253513},
issn = {1945-0826},
abstract = {BACKGROUND: Asian Americans are severely underrepresented in Alzheimer disease and related dementias research, and the cognitive aging of Asian Indians in the United States is poorly understood. There is a pressing need to bridge the gap in the literature concerning dementia and cognitive impairment among Asian Indians to reduce the current disparities. This study examines how knowledge, beliefs, and attitudes shape dementia disparities among older Asian Indian immigrants in the United States.

METHODS: In-depth interviews were conducted with Asian Indian adults, ages 50 years and older, who immigrated from India to the United States. Participants were recruited through cultural and faith-based organizations by using flyers and social media advertisements. Interviews explored perceptions of dementia and aging, barriers to receiving care, and beliefs related to aging. Interviews were audio-recorded and transcribed, and inductive thematic analysis was conducted by 2 investigators.

RESULTS: Participants (n=29) were mostly women (73%) and 65-74 years old (38%) and had been in the United States for an average of 35 years. Cognitive impairment and dementia were viewed as natural functions of aging, and participants were unaware of screening methods to detect cognitive impairment early. Participants perceived dementia as more prevalent among Asian Indians living outside of India due to loss of social support.

CONCLUSION: Overall, this study shows challenges and opportunities to advancing culturally appropriate cognitive aging care among Asian Indian immigrants in the United States. Findings from this study provide valuable insights into this underresearched area and can inform culturally sensitive interventions and policies to support the cognitive health of Asian Indian immigrants as they age.},
}

@article {pmid42253730,
year = {2026},
author = {Gao, PP and Zhou, FL and Zheng, GB and Liu, YL and Cheng, SJ and Ye, ZW and Liang, YT and Liu, L and Guo, LQ and Lin, JF},
title = {Ergothioneine-rich water extracts of Hericium erinaceus HE-17 alleviate Alzheimer's disease in mice by regulating oxidative stress, inflammation, and the gut microenvironment.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1835714},
pmid = {42253730},
issn = {2296-861X},
abstract = {Alzheimer's disease (AD) imposes a significant global disease burden, necessitating simple dietary interventions to prevent or delay disease progression. However, the neuroprotective effects of ergothioneine (EGT)-rich natural extracts as dietary supplements remain largely unexplored. This study aimed to screen a high EGT-producing Hericium erinaceus strain (HE-17) from 29 isolates, optimize its culture conditions and amino acid supplementation using single-factor and orthogonal experiments, and evaluate the neuroprotective effects of its extract in an APP/PS1 transgenic mouse model. Cognitive function, neuronal damage, inflammation, oxidative stress, and gut microbiota composition were assessed using the Morris Water Maze test, histopathology, immunofluorescence, biochemical assays, enzyme-linked immunosorbent assay (ELISA), and 16S rRNA gene sequencing. The results showed that the water extract of H. erinaceus HE-17 (WEH) contained 2.57 ± 0.14 mg/g EGT and exhibited no acute toxicity in mice. High-dose WEH (2 g/kg BW/d, containing 5.76 mg/kg EGT), low-dose WEH (0.50 g/kg BW/d, containing 1.44 mg/kg EGT), and pure EGT (1.44 mg/kg), administered for 90 days, were found to improve cognitive function and enhance spatial learning and memory, while reducing Aβ aggregation and tau phosphorylation. Meanwhile, WEH supplementation was associated with decreased pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in both the brain and serum. It also reduced oxidative stress markers while increasing antioxidant indicators in brain tissue, with the high-dose group showing the most pronounced effects in APP/PS1 mice. Gut microbiota analysis revealed that low-dose WEH was associated with a reduced abundance of Fusobacteriota and Proteobacteria and an increased abundance of Lactobacillus. These findings suggest that WEH may help mitigate AD-related pathological changes in APP/PS1 mice.},
}

@article {pmid42253927,
year = {2026},
author = {Frosina, M and Maurotti, S and Castagna, A and Montalcini, T and Pujia, A and Tirinato, L},
title = {Beyond the Known and Established Neurodegenerative Effects: Roles of APOE Across a Wide Spectrum of Pathophysiological Condition.},
journal = {MedComm},
volume = {7},
number = {6},
pages = {e70789},
pmid = {42253927},
issn = {2688-2663},
abstract = {Apolipoprotein E (ApoE) is classically recognized for its role in lipid trafficking and the coordination of lipoprotein metabolism, yet its influence extends well beyond these pathways. While the contribution of ApoE isoforms to neurodegenerative disorders, most notably Alzheimer's disease, has been described in considerable detail, their impact on peripheral physiology is far less clearly defined. Evidence accumulated over the past decade suggests that variation in ApoE may shape traits such as adiposity, fat and lean mass distribution, bone density, muscle function, and cardiovascular risk, although the findings are often inconsistent across studies and populations. This review brings together current knowledge on how ApoE interfaces with several key biological processes, including inflammatory signaling, glucose and insulin responses, mitochondrial and redox homeostasis, senescence, and regulated cell death. These pathways lie at the core of many chronic disorders, yet their links to ApoE genotype remain insufficiently defined. Moreover, translation of these findings, including the use of ApoE genotyping for risk stratification, therapeutic choices, and personalized prevention is also discussed. By reframing ApoE as a systemic regulator rather than a brain-restricted factor, this review offers a cohesive roadmap for interdisciplinary research and improved clinical interpretability of ApoE-associated risk.},
}

@article {pmid42253956,
year = {2026},
author = {Wu, Y and Lyu, W and Xie, X and Fu, X and Zhang, L and Pan, J},
title = {The tango of immune and neural cells: orchestrating neuroinflammation mediated brain disorders.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1827437},
pmid = {42253956},
issn = {1664-3224},
abstract = {The bidirectional interaction between immune cells and neural cells is the core effector unit of neuroinflammation, determining whether the central nervous system (CNS) maintains homeostasis or develops disease. Under physiological conditions, this interaction supports CNS homeostasis through microglial surveillance, astrocytic metabolic support (including the astrocyte-neuron lactate shuttle and glutamate reuptake), and blood-brain barrier (BBB) integrity. Under pathological states, dysregulated immune-neural crosstalk drives neuroinflammation. Damaged neurons activate microglia and astrocytes, which in turn secrete proinflammatory factors that impair neurons, reduce neurotrophic support, and disrupt BBB integrity. This interaction operates through cell surface receptor-ligand systems and soluble signals. Representative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), depression, and schizophrenia share common inflammatory features such as glial cell activation, BBB damage, and synaptic dysfunction, while exhibiting disease-specific pathological mechanisms. Clinical translation progress has been made in developing biomarkers for diagnosis, targeting immune cells and neural cells for therapy, and exploring emerging interventions like immunometabolic regulation and cell therapy. However, gaps remain in understanding cell type specificity, spatiotemporal dynamics, and achieving precise clinical application. Future interdisciplinary research will further advance the role of immune-neural interaction as a key target for preventing and treating neurological diseases, providing more precise diagnostic and therapeutic strategies.},
}

@article {pmid42253968,
year = {2026},
author = {Feng, P and Zhang, W and Zhao, Y and Zhao, P and Li, E},
title = {Synthetic microbial communities: a novel emerging models for dissecting gut microbiota-host interactions in neurodegenerative diseases.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1822743},
pmid = {42253968},
issn = {1664-3224},
abstract = {The gut-brain axis (GBA) has emerged as a critical regulatory pathway underlying the pathogenesis of neurodegenerative diseases (NDs) such as Alzheimer's disease and Parkinson's disease. However, the high complexity and individual variability of native gut microbiotas hinder the precise elucidation of causal relationships between specific microbial taxa, their metabolites, and host neuroinflammatory or neurodegenerative processes. Synthetic microbial communities (SynComs), consisting of defined and reproducible bacterial strains, have recently emerged as powerful experimental models to overcome these limitations. This review summarizes the applications of SynComs in dissecting GBA crosstalk in NDs, highlighting their utility in validating key microbial mediators, deciphering molecular signaling pathways (e.g., microbial metabolite-brain barrier interactions, immune cell activation), and evaluating therapeutic strategies targeting the gut microbiota. By reducing community complexity while retaining core functional traits, SynComs enable controlled in vitro and in vivo studies that bridge the gap between observational microbiome profiling and mechanistic insights. Furthermore, the customization of SynComs allows for mimicking disease-specific microbial dysbiosis, facilitating the identification of novel therapeutic targets for NDs. Collectively, SynComs represent an innovative and standardized tool to advance our understanding of gut microbiota-host interactions in neurodegeneration and accelerate the development of microbiome-based interventions.},
}

@article {pmid42254080,
year = {2026},
author = {Maleki, Z and Mirshekar, MA and Montazerifar, F and Etminani, B and Keykha, F},
title = {Time-Restricted Feeding Preserves Synaptic Function and Modulates Reelin and α-Synuclein in an Acute Amyloid-β Rat Model: A Comparative Study With Alternate-Day Fasting.},
journal = {Journal of nutrition and metabolism},
volume = {2026},
number = {},
pages = {7185647},
pmid = {42254080},
issn = {2090-0724},
abstract = {INTRODUCTION: Alzheimer's disease (AD), a major neurodegenerative disorder, is characterized by progressive cognitive decline and the accumulation of amyloid-beta and tau proteins in the brain. Intermittent fasting (IF) is being explored as a dietary intervention to mitigate AD-related effects, possibly by modulating factors such as reelin and α-synuclein, which are involved in synaptic function and AD pathology.

METHODS: The study included six groups of rats: Ctrl, Ctrl.ADF, Ctrl.TRF, AD, AD.TRF, and AD.ADF. AD was induced by bilateral ICV injections of 5 μL Aβ. To prove fasting, blood glucose levels were assessed with a glucometer. Memory and learning were assessed using the Morris Water Maze (MWM) test, and hippocampal reelin and α-synuclein concentrations were quantified via ELISA. Electrophysiological recordings were analyzed using eProbe software.

RESULTS: TRF was more effective than ADF in improving cognitive function in AD rats, as indicated by a significant increase in TSGQ [F (5,40) = 5.590, p < 0.01] and swimming speed [F (3,21) = 114.3, p < 0.01], along with a significant reduction in latency time and path length (p < 0.001). Both TRF and ADF significantly increased reelin concentration and neuronal firing rate (p < 0.01), whereas only TRF led to a significant decrease in α-synuclein levels.

DISCUSSION: These findings suggest that TRF may enhance spatial memory and reduce α-synuclein accumulation in AD rats, possibly through mechanisms associated with synaptic plasticity and neuroprotection.},
}

@article {pmid42254102,
year = {2026},
author = {Khan, SA and Qamar, MA and Ali, T},
title = {Ferroptosis at the crossroads of epilepsy and neurodegeneration.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3874-3875},
pmid = {42254102},
issn = {2049-0801},
abstract = {Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a potential contributor to neuronal injury across neurological disorders. Increasing evidence suggests that ferroptotic mechanisms may participate in the pathophysiology of epilepsy, linking sustained oxidative stress, iron dysregulation, and progressive neuronal loss. Mechanistically, ferroptosis is driven by disruption of the canonical system Xc[-]-glutathione-glutathione peroxidase 4 axis, resulting in impaired detoxification of lipid hydroperoxides and membrane damage accumulation. Neurons are particularly susceptible due to high oxygen consumption, abundant polyunsaturated fatty acids, and vulnerability to iron-catalyzed reactive oxygen species generation. Experimental studies and gene expression analyses have identified ferroptosis-related pathways enriched in epileptic tissue, while human biomarker investigations demonstrate reduced glutathione levels and elevated lipid peroxidation products in patients with epilepsy. Although most therapeutic data derive from preclinical rodent models, pharmacological modulation of ferroptosis - via iron chelation or inhibition of lipid peroxidation - has shown seizure-reducing and neuroprotective effects. Importantly, ferroptosis likely operates alongside other regulated cell death pathways rather than acting as a singular mechanism. Shared features of iron accumulation and lipid peroxidation in neurodegenerative diseases, such as Alzheimer's and Parkinson's, further support a broader pathogenic relevance. Continued translational investigation is necessary to determine whether targeting ferroptosis may offer disease-modifying strategies in epilepsy.},
}

@article {pmid42254130,
year = {2026},
author = {Adnan, H and Adnan, E and Kamgang, JS},
title = {The emerging link between shingles vaccination and reduced Alzheimer's risk: a public health signal for viral-dementia pathways.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3899-3900},
pmid = {42254130},
issn = {2049-0801},
}

@article {pmid42254138,
year = {2026},
author = {Faisal, AR and Singh, P and Hassan, M and Laiba, F and Zaman, A and Hafeez, AS and Abdullah, and Faizan, M and Ashraf, MU and Zahoor, M and Alam, MM and Maity, R and Dhali, A},
title = {Demographic trends in mortality related to Alzheimer's disease and pneumonia: a two-decade (1999-2022) analysis from the CDC WONDER database.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3076-3084},
pmid = {42254138},
issn = {2049-0801},
abstract = {BACKGROUND AND AIMS: Pneumonia is a leading cause of death among Alzheimer's disease (AD) patients, often due to complications like sepsis or respiratory failure. This study aims to analyze the joint mortality patterns of AD and pneumonia to provide an accurate update on the public health impact and help uncover modifiable factors that could mitigate the disease burden.

METHODS: In this retrospective observational study, deidentified CDC WONDER death certificate data (1999-2022) were analyzed for individuals aged 65+ with ICD-10 codes for AD (G30) and pneumonia (J09-J18). To identify cases of AD and pneumonia, death records from the Multiple Causes of Death Public Use registry were reviewed, with these conditions listed as either a contributing or underlying cause of death. Mortality rates were calculated, and trends were evaluated using the Joinpoint Regression Program (National Cancer Institute).

RESULTS: From 1999 to 2022, the overall mean age-adjusted mortality rate (AAMR) for AD- and pneumonia-related deaths was 21.33 (95% CI: 17.91-24.75). The AAMR declined significantly from 37 in 1999 to 11.32 in 2016 (APC: -7.20, 95% CI: -12.97 to -5.47; P = 0.03) and then remained stable until 2022 (APC: -0.79, P = 0.88). Males consistently had higher mortality (mean AAMR: 22.57) than females (20.39), with a notable decline in male AAMR from 42.36 in 1999 to 10.43 in 2022, and female AAMR from 33.81 to 8.58. Racial disparities were evident: NH Whites had the highest mean AAMR (22.21), followed by Hispanics (17.51), NH Blacks (14.81), and NH Asians (13.62). Regionally, the West had the highest AAMR (26.32), while the Northeast had the lowest (16.39). Metropolitan AAMR decreased significantly from 2004 to 2018 (APC: -8.41), while non-metropolitan areas showed a slower decline with a slight rise post-2018.

CONCLUSION: Significant disparities in AD and pneumonia mortality highlight the need for targeted, community-focused interventions.},
}

@article {pmid42254613,
year = {2026},
author = {Kassymzhanova, M and Shonbay, K and Shikhova, OM and Raspopova, N and Karibayeva, I},
title = {Depression as a prognostic factor for conversion from mild cognitive impairment to all-cause dementia and Alzheimer's disease: a systematic review and meta-analysis of longitudinal studies.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1831762},
pmid = {42254613},
issn = {2296-2565},
abstract = {BACKGROUND: Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia, with annual conversion rates to Alzheimer's disease (AD) or all-cause dementia estimated at 10%-15%. The role of depression as a prognostic factor for dementia progression remains unclear. This systematic review and meta-analysis aimed to clarify the association between depression and risk of conversion from MCI to AD and all-cause dementia.

METHODS: We conducted a systematic review and meta-analysis of longitudinal cohort studies following PRISMA 2020 guidelines. PubMed, PsycINFO, Web of Science, and Scopus were searched. Eligible studies included adults with MCI, depression assessed by clinical diagnosis or validated scales, and reported hazard ratios (HRs) for progression to dementia. Random-effects meta-analyses were performed for unadjusted and adjusted HRs. Risk of bias was assessed using the Newcastle-Ottawa Scale, and certainty of evidence was evaluated with GRADE.

RESULTS: Seventeen studies were included, with follow-up ranging from 6 months to 12 years. In unadjusted analyses, baseline depression was associated with increased risk of progression overall (HR 1.66, 95% CI 1.22-2.26); however, heterogeneity across studies was high (I [2] = 99.1%), limiting confidence in the pooled estimate. The association was significant for progression to AD (HR 1.57, 95% CI 1.15-2.15; I [2] = 99.4%), but not for all-cause dementia (HR 1.95, 95% CI 0.85-4.48; I [2] = 90%). In adjusted analyses, depression remained associated with increased progression risk overall (HR 1.21, 95% CI 1.05-1.39), with high heterogeneity (I [2] = 99.8%). The association was statistically significant for all-cause dementia (HR 1.24, 95% CI 1.01-1.52; I [2] = 78.8%), but not for AD (HR 1.18, 95% CI 0.95-1.47; I [2] = 99.8%). Sensitivity analyses confirmed robustness of findings, and publication bias was not detected. Certainty of evidence was rated very low due to heterogeneity.

CONCLUSION: Depression appears to be associated with an increased risk of progression from MCI to dementia; however, the very high heterogeneity and very low certainty of evidence substantially limit confidence in the magnitude and consistency of this association. These findings highlight the importance of depression screening and management in MCI populations. Integrating mental health care into cognitive disorder clinics may improve patient outcomes and potentially delay dementia onset.

identifier: CRD420261308245.},
}

@article {pmid42254706,
year = {2026},
author = {Barczak, A},
title = {Diagnostic utility of Addenbrooke's Cognitive Examination III in differentiating Alzheimer's disease dementia, vascular dementia, and mixed dementia.},
journal = {Postepy psychiatrii neurologii},
volume = {35},
number = {2},
pages = {85-93},
pmid = {42254706},
issn = {2720-5371},
abstract = {PURPOSE: Differentiating between Alzheimer's disease (AD), vascular dementia (VaD), and mixed dementia (MD) remains a major clinical challenge, as overlapping symptoms and comorbid pathologies limit the diagnostic value of screening tools. The Addenbrooke's Cognitive Examination III (ACE-III) offers a multidomain assessment and may support differential diagnosis.

METHODS: The study included 138 Polish patients with mild dementia (46 AD, 46 VaD, 46 MD), matched for age, sex, and education, and diagnosed based on current clinical criteria. Group comparisons were conducted using the Kruskal-Wallis test with Dunn- Bonferroni post hoc analyses.

RESULTS: Total ACE-III scores did not differ significantly between the groups. Significant effects were observed only in the Memory domain, where VaD patients scored higher than both AD and MD, who did not differ from each other. Subtest analyses confirmed group differences in episodic memory tasks. Only Serial 7 Subtraction (Attention) and Letter Fluency differentiated between groups, with AD patients outperforming VaD patients. Within the Visuospatial domain, only Dot Counting differentiated between groups (AD > MD > VaD). The Language domain showed no group effects.

CONCLUSIONS: While total ACE-III scores have limited diagnostic value, domain- and subtest-level analyses reveal distinct cognitive profiles supporting differential diagnosis. VaD is marked by preserved episodic memory but impaired attention and executive tasks, AD by severe episodic memory deficits, and MD by an AD-like profile with vascular contributions. Domain-focused interpretation of ACE-III may enhance diagnostic accuracy in clinical practice.},
}

@article {pmid42254726,
year = {2026},
author = {Tsengele, N and Sodi Magudigana, A and Gikelekele, G and Epenge, E and Kangula, G and Vukumuna, EM and Bilongo, AM and Mbuku Nguala, S and Bomba, DB and Mananga Lelo, G and N'situ Mankubu, A and Ikanga, J},
title = {Association between neurodegenerative plasma biomarkers and geriatric depression in older adults with and without clinical dementia in Kinshasa, Democratic Republic of the Congo.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1787247},
pmid = {42254726},
issn = {1664-0640},
abstract = {INTRODUCTION: Previous Western studies have shown an association between neurodegenerative plasma biomarkers and geriatric depression. However, few studies have examined this relationship in sub-Saharan African countries. This article examines this association in older adults with or without clinical dementia in Kinshasa, Democratic Republic of Congo.

METHODS: This cross-sectional study included eighty-one people aged 65 years and older assessed for dementia using the Community Dementia Screening Instrument (CSID) and the Alzheimer's Disease Questionnaire. Depression and cognitive impairment were assessed using the Geriatric Depression Scale and the African Neuropsychological Battery (ANB), respectively. Plasma biomarkers measured included β-amyloid (Aβ) 40/42, phosphorylated tau 181 (p-tau), neurofilament light chain (NfL), glial fibrillar acid protein (GFAP), interleukins (IL-1β, IL-10), and tumor necrosis factor-α (TNF-α). Logistic regression models were used to estimate the likelihood that these biomarkers are associated with depression, adjusting for sex, age, and education level.

RESULTS: The mean age of the participants was 72.9 years. Of those suspected of suffering from Alzheimer's disease (AD), 80% had geriatric depression. High blood pressure was common in participants with suspected AD (60%). People with dementia had significantly lower cognitive scores on all ANB tests than those without dementia. GFAP and NfL were significantly associated with higher odds of geriatric depression, with odds ratios of 1.98 (1.17-3.67; p = 0.02) and 1.76 (1.06-3.20; p = 0.04), respectively. Other biomarkers were not associated with depression.

CONCLUSION: This study suggests a potential role of nonspecific biomarkers of AD, neurodegeneration, and astrocytic glial activation in geriatric depression in older adults in sub-Saharan Africa.},
}

@article {pmid42254757,
year = {2026},
author = {O'Brien, K and Coykendall, C and Harkins, K and Wang, X and Perelman, A and Zhang, M and Karlawish, J},
title = {Study of the utility and impact of a plasma p-tau181 Alzheimer's biomarker (SUITABLE).},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {1},
pages = {e70207},
pmid = {42254757},
issn = {2352-8737},
abstract = {INTRODUCTION: Blood-based Alzheimer's disease (AD) biomarkers are increasingly used in clinical care, but there are few real-world studies of their clinical utility. We evaluated the impact of plasma phosphorylated tau at threonine 181 (p-tau181) on the diagnosis and management of patients with cognitive impairment in a memory clinic.

METHODS: Dementia specialists referred patients for plasma p-tau181 testing during clinical care. We used surveys and chart review to assess the impact of plasma p-tau181 testing on clinical care and patient and care partner wellbeing. We assessed co-primary outcomes of (1) change in diagnostic confidence before vs after testing, (2) change in diagnosis, and (3) change in management. A diagnosis or management change of greater than 30% was considered to be clinically significant. Secondary and exploratory outcomes included impact of plasma p-tau181 testing on the use of additional diagnostics and impact on patient and care partner psychological wellbeing, health behaviors, and future planning.

RESULTS: One hundred patients completed plasma p-tau181 testing; 81% had an elevated result, and 19% had a non-elevated result. Clinician diagnostic confidence averaged 1.43 points higher after p-tau181 testing (95% confidence interval [CI] 1.02 to 1.84, p < 0.0001). After testing, 27.7% (95% CI 18.9% to 36.4%, p = 0.31) of patients had a change in management and 17.2% of patients had a change in diagnosis - significantly lower than the 30% threshold (95% CI 9.5% to 24.9%, p = 0.004). Patients with elevated results were less likely to have a diagnosis changed after testing than those with non-elevated results (OR 0.08 [95% CI 0.01 to 0.47], p = 0.005). A non-elevated result was associated with decreased use of amyloid positron emission tomography (PET) (odds ratio [OR] 0.25 [95% CI 0.07 to 0.86], p = 0.028). Patients with an elevated result had higher anxiety at 2 to 3 months after disclosure (p = 0.01).

DISCUSSION: Non-elevated plasma p-tau181 results impacted the diagnosis and use of amyloid PET imaging in a memory clinic. There was increased anxiety in patients after testing, affirming the need for post-disclosure psychological support.},
}

@article {pmid42254865,
year = {2026},
author = {Jannah, AR and Hasegawa, M and Ham, J and Hara, N and Tsukie, T and Obinata, A and Kikuchi, M and Kasuga, K and Yamaguchi, H and Hamasaki, H and Tada, M and Kakita, A and Matsumoto, M and Miyashita, A and Ikeuchi, T},
title = {Mass spectrometry-based proteomic profiling of human tauopathy brains suggests mitochondria-associated alterations.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1815858},
pmid = {42254865},
issn = {1662-5099},
abstract = {Tauopathies are neurodegenerative disorders characterized by intracellular accumulation of abnormal tau encoded by MAPT, yet their molecular mechanisms remain incompletely understood. We aimed to identify proteomic signatures associated with the primary tauopathies corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), as well as the secondary tauopathy Alzheimer's disease (AD), and to characterize their interaction networks. Total homogenates from the specified cortical region of postmortem brains of AD (n = 4), CBD (n = 4), PSP (n = 4), and control (n = 4) subjects were analyzed by mass spectrometry (MS). Differentially expressed proteins were subjected to functional enrichment and protein-protein interaction (PPI) network analyses. Reproducibility was assessed using JESS-based western blotting (WB), and selected candidates were examined by immunohistochemistry (IHC) and single-nucleus RNA sequencing (snRNA-seq) to evaluate cell-type-specific transcriptomic profiles. In the four-group comparison, 859, 114, 6, and 1 proteins showed P FDR < 0.05, < 0.01, < 0.005, and < 0.001, respectively. Six proteins (AK3, ATP5PD, COX7C, PPA1, PREP, and UQCRC1) with P FDR < 0.005 formed a highly interconnected network enriched for mitochondrial pathways, including oxidative phosphorylation and respiratory electron transport. WB validation showed strong concordance for four proteins (AK3, PREP, PPA1, and ATP5PD). IHC confirmed neuronal expression of PPA1 and PREP and revealed prominent microglial PPA1 immunoreactivity in PSP brains. snRNA-seq provided complementary cell-type-specific transcriptomic alterations. These findings suggest mitochondria-associated molecular changes shared across primary and secondary tauopathies; however, given the exploratory nature of this study, these observations should be interpreted cautiously and considered hypothesis-generating, warranting further investigation.},
}

@article {pmid42254957,
year = {2026},
author = {Huang, YY and Li, LL and Yao, RX and Dong, JZ and Gan, YH and Chen, YL and Chen, KL and Chen, SF and Yuan, MY and Xin, JW and Wang, J and Zhang, YR and Wang, Y and Yen, TC and Cui, M and Guo, Y and Yu, JT},
title = {Plasma p-Tau217 improves diagnostic accuracy and clinician confidence in cognitive disorder classification.},
journal = {Innovation (Cambridge (Mass.))},
volume = {7},
number = {6},
pages = {101272},
pmid = {42254957},
issn = {2666-6758},
abstract = {The clinical utility of plasma phosphorylated tau at threonine 217 (p-tau217) levels as a diagnostic tool for cognitive disorders in real-world settings remains uncertain. In this cross-sectional retrospective study, 738 consecutive subjects presenting with cognitive complaints at a memory clinic underwent diagnostic evaluation incorporating plasma p-tau217 alongside standard clinical assessments ("tier 2": routine neuroimaging and cognitive testing) and advanced biomarker testing ("tier 1": amyloid positron emission tomography [PET] imaging or cerebrospinal fluid [CSF] analysis). Diagnostic impact and confidence were assessed using clinician surveys. Incorporating plasma p-tau217 into the routine tier 2 diagnostic workup significantly influenced clinical decision-making, leading to diagnostic revisions in 30.2% of cases and improving overall diagnostic confidence from 65.1% to 79.4%. Plasma p-tau217 demonstrated high diagnostic accuracy for Alzheimer's disease (AD), with a sensitivity of 0.88 and a specificity of 0.84. Notably, its specificity was superior to tier 2 diagnoses, whereas its sensitivity did not differ significantly. Plasma p-tau217 also exhibited non-inferior performance to tier 1 approaches in the diagnostic distribution of AD, though with marginally lower diagnostic confidence. For non-AD diagnoses, plasma p-tau217 significantly impacted the classification of synucleinopathies and performed comparably to tier 1 methods. In conclusion, plasma p-tau217 meaningfully impacted diagnostic precision and confidence in subjects presenting to a real-world memory clinic, offering a minimally invasive, cost-effective, and accessible alternative to state-of-the-art examinations. As the global population ages and cognitive disorders become more prevalent, the integration of plasma p-tau217 into routine practice has the potential to streamline diagnostic workflows and enhance the efficient utilization of medical resources.},
}

@article {pmid42255923,
year = {2026},
author = {Lin, M and Chiotis, K and Maiti, P and Zhang, J and Blazhenets, G and Rocha, S and Shankar, R and Amuiri, A and Hammers, DB and Eloyan, A and Kirby, K and Koeppe, RA and Aisen, P and Beckett, L and Kukull, WA and Toga, AW and Atri, A and Clark, DG and Day, GS and Duara, R and Graff-Radford, NR and Grant, I and Honig, LS and Johnson, ECB and Jones, DT and Masdeu, JC and Mendez, MF and Musiek, E and Onyike, CU and Riddle, M and Rogalski, E and Salloway, S and Sha, SJ and Turner, RS and Wingo, TS and Wolk, DA and Womack, KB and Nudelman, KNH and Touroutoglou, A and Jack, CR and Vemuri, P and Vogel, JW and Dufault, SM and Hoffmann, TJ and Carrillo, MC and Dickerson, BC and Apostolova, LG and Rabinovici, GD and La Joie, R},
title = {Tau topography subtypes account for clinical heterogeneity and longitudinal trajectories in early-onset Alzheimer's disease.},
journal = {Brain communications},
volume = {8},
number = {3},
pages = {fcag176},
pmid = {42255923},
issn = {2632-1297},
abstract = {The growing availability of large-scale biomarker datasets has allowed data-driven methods to characterize Alzheimer's disease biological heterogeneity. However, most prior studies have focused on cohorts of late-onset amnestic cases, leaving early-onset Alzheimer's disease underexplored. We aimed to characterize tau-PET-based subtypes through a robust data-driven approach in the Longitudinal Early-Onset Alzheimer's Disease Study. Baseline [[18]F]Flortaucipir PET scans from 365 amyloid-PET-positive participants with sporadic early-onset Alzheimer's disease were quantified in the left and right medial temporal, lateral temporal, occipital, parietal, and frontal cortices. Tau PET values were z-scored against 85 amyloid-PET-negative cognitively normal age-matched participants and fitted into Subtype and Stage Inference (SuStaIn)-an unsupervised clustering algorithm that simultaneously models subtypes and progression from cross-sectional data. The derived subtypes were subsequently characterized by baseline and longitudinal clinical, cognitive, MRI, tau and amyloid PET features. We identified three tau-PET-based subtypes: on average, Subtype 1/Typical (n = 144, 40%) showed a predominant bilateral temporoparietal pattern typical of Alzheimer's disease. Subtype 2/Left temporal (n = 111, 31%) showed predominant left temporal binding. Subtype 3/Posterior (n = 104, 29%) showed early and permeating occipitoparietal involvement. Subtypes did not differ in demographics or global amyloid burden, but were relatively more enriched for specific clinical presentations: S1/Typical for amnestic presentations, S2/Left Temporal for primary progressive aphasia, and S3/Posterior for posterior cortical atrophy. Baseline tau PET subtypes aligned with cortical atrophy patterns and domain-specific cognitive impairment. When follow-up tau PET scans were fitted to SuStaIn trained on baseline data, 85.6% (n = 172/201) of participants retained the same subtype classification, indicating subtype temporal stability, and progressed within subtypes by 0.56 ± 0.70 SuStaIn stage/year. Longitudinal voxel-wise linear mixed-effects modelling revealed tau accumulation patterns for each subtype in regions relatively spared at baseline: occipital lobe accumulation predominated in S1/Typical, bilateral frontal and right temporal in S2/Left Temporal, and bilateral frontotemporal lobes in S3/Posterior. All subtypes showed longitudinal increases in Clinical Dementia Rating-Sum of Boxes, but with slower worsening in S3/Posterior compared with the other subtypes. Our findings reveal robust subtypes in sporadic early-onset Alzheimer's disease characterized by distinct spatiotemporal tau patterns that parallel differences in clinical presentations and trajectories of neurodegeneration. These subtypes extend beyond traditional clinical syndromes and support a more nuanced framework for individualized prognosis and care. Incorporating tau PET subtyping into clinical trial design could enable more targeted therapeutic approaches for this younger population.},
}

@article {pmid42255935,
year = {2026},
author = {Majdic, G},
title = {The triple-hit hypothesis of Alzheimer's disease: blood-brain barrier breakdown, infection, and neuroimmune activation as a unified etiological framework.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1815976},
pmid = {42255935},
issn = {1662-4548},
abstract = {Studies of Alzheimer's disease (AD) have long been dominated by the amyloid cascade hypothesis, although mounting evidence suggests that amyloid-β (Aβ) deposition might be a late downstream event, rather than the initiating trigger of AD. Here, I propose a unifying Triple-Hit Hypothesis in which AD develops through a sequential interaction among three causative processes that have been individually implicated before in the onset of Alzheimer's disease: (1) early blood-brain barrier (BBB) breakdown, (2) entry or reactivation of microbial agents within the brain, and (3) maladaptive innate immune responses that produce chronic neuroinflammation and Aβ accumulation. Converging data from human imaging, neuropathology, infectious disease studies, genetics, and vascular medicine could suggest that these three processes, which were in some previous studies linked to AD, might not be independent but rather that their temporal synergy could drive disease progression. This new conceptual framework integrates long-standing but fragmented lines of evidence and, if confirmed by experimental studies, offers the possibility for the development of new diagnostic biomarkers, new therapeutic entry points, and prevention strategies for AD. I argue that understanding AD as a disorder of the blood-brain barrier, immunity, and host-pathogen interactions should be taken into account in future research on the etiology and clinical progression of AD.},
}

@article {pmid42255951,
year = {2026},
author = {Najmi, Z and Dharmapuri, A and Contreras, JA and Hayes, CA and , },
title = {Associations of plasma p-Tau217 with cognitive domain performance in clinically unimpaired participants: Evidence from HABS-HD.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70370},
pmid = {42255951},
issn = {2352-8729},
abstract = {INTRODUCTION: The relationship between plasma phosphorylated tau 217 (p-Tau217) and domain-specific cognitive performance across race and ethnic groups remains unclear.

METHODS: We analyzed data from 2052 clinically unimpaired participants from the Health & Aging Brain Study-Health Disparities cohort. Using adjusted multivariable linear regressions, we evaluated the associations between p-Tau217 and cognitive scores (immediate and delayed memory, attention/processing speed, executive function, and language). Analyses were conducted in the overall sample, stratified by race and ethnicity, and in an age- and sex-matched subsample (n = 1032).

RESULTS: Plasma p-Tau217 levels were lower in Non-Hispanic Black (NHB) and Hispanic participants (p < 0.001) despite lower cognitive scores (p < 0.001). Higher p-Tau217 was associated with worse cognition overall (β -0.05 to -0.11). Associations were strongest in Non-Hispanic White (NHW), limited in NHB, and domain-specific in Hispanic groups. Matched analyses attenuated effects.

DISCUSSION: Plasma p-Tau217 is associated with domain-specific cognitive performance in clinically unimpaired individuals, but these associations vary across racial and ethnic groups.},
}

@article {pmid42255952,
year = {2026},
author = {Sonson, M and Yadollahikales, G and Flores, A and Lasner, I and Lee, S and Tan, Z and Quach, C and Kremen, S},
title = {From clinical trial to clinical experience: Lecanemab therapy in a real-world case series.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70365},
pmid = {42255952},
issn = {2352-8729},
abstract = {The approval of anti-amyloid therapies has expanded therapeutic options for patients with Alzheimer's disease (AD), but the pivotal trials that proved their efficacy restrict their applicability to a selected patient population. We describe a case series of seven patients with biomarker-confirmed AD pathology evaluated in an academic memory clinic and treated with lecanemab whose characteristics would have disqualified them from trial participation. Patient histories and outcomes are presented, accompanied by description of the clinical team's reasoning and application of published Appropriate Use Recommendations for each case. Overall, lecanemab was largely well tolerated, with no unexpected safety concerns and amyloid-related imaging abnormality rates comparable to trial data. Clinically, most patients remained stable over the treatment period, though some continued to decline. This series highlights the challenges and considerations in applying disease-modifying therapies beyond trial populations, emphasizing the need for real-world data to guide treatment in diverse AD presentations.},
}

@article {pmid42255953,
year = {2026},
author = {Wallace, A and Zhou, O and Hoang, MN and Porter, G and Padilla, C and Marshall, C},
title = {Lecanemab and amyloid-related imaging abnormalities: Real-world data from a single center experience.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70377},
pmid = {42255953},
issn = {2352-8729},
abstract = {INTRODUCTION: Lecanemab has demonstrated both safety and efficacy in clinical trials; however, routine clinical data are sparse. We contribute to the growing body of real-world safety data, with a special focus on amyloid-related imaging abnormalities (ARIA).

METHODS: We conducted a retrospective chart review of 146 patients treated with lecanemab according to appropriate-use recommendations at a specialty memory center clinic.

RESULTS: Real-world safety and efficacy data closely resemble published data in the Clarity-AD trial. Thirty-three patients (23%) discontinued treatment; all remaining patients completed at least 12 months of treatment. We observed a positive trend toward increasing ARIA edema/effusion (ARIA-E) with increasing mean arterial pressure and a mean amyloid clearance of -90.6 at 18 months.

DISCUSSION: When used according to appropriate-use recommendations, lecanemab is as safe as reported in the Clarity-AD trial. Further investigation into real-world data is necessary for a more complete evaluation of lecanemab's safety and efficacy.},
}

@article {pmid42255955,
year = {2026},
author = {Krakauer, CA and Reilly, L and Su, YR and Walker, RL and Lee, D and Xaiyamuangchanh, VA and Cronkite, DJ and Gatto, NM and Crane, PK and Chew, EY and Arterburn, DE and Lee, CS},
title = {Age-related macular degeneration severity and risk of Alzheimer's disease in older adults in a prospective, community-based cohort study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70368},
pmid = {42255955},
issn = {2352-8729},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is associated with higher risk of Alzheimer's disease (AD), but how AD risk changes as AMD progresses remains unclear.

METHODS: Among participants in the Adult Changes in Thought study, we characterized the worst dry and wet AMD severities experienced to date on a scale of 0 to 10 and assessed whether they were associated with AD risk.

RESULTS: Among 2611 participants (550 AD cases, median 6.8 years follow-up), AD hazard was estimated to increase by 4% per one unit increase in dry and wet scores (dry: 95% confidence interval [CI] for hazard ratio [HR] 1.01 to 1.07, p = 0.01; wet: 95% CI 1.00 to 1.08, p = 0.03). HR estimates were similar among people without diagnosed AMD and were attenuated among those with diagnosed AMD.

DISCUSSION: Worse AMD severity was associated with higher AD risk, with severity scores potentially offering greater clinical utility for AD risk characterization among individuals without diagnosed AMD.},
}

@article {pmid42255956,
year = {2026},
author = {Hazan, J and Mealing, M and Mittelman, E and Godsell, S and Roche, S and Lorencatto, F and Rapaport, P and Keshavan, A and Schott, JM and Howard, R},
title = {Perceptions of the use of biomarkers for Alzheimer's disease diagnosis: A systematic review and synthesis of the qualitative literature.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70380},
pmid = {42255956},
issn = {2352-8729},
abstract = {Biomarker investigations are increasingly used in the diagnostic assessment of Alzheimer's disease (AD), yet stakeholder perceptions and implementation factors remain underexplored. No systematic qualitative synthesis exists on these views. This systematic review aimed to synthesize the qualitative literature on perceptions of diagnostic AD biomarker investigations in both clinical and research settings among individuals with cognitive impairment, caregivers, and health-care professionals (HCPs) and to identify barriers and enablers to their practical implementation. A systematic review searched four databases up to May 2025 for English-language qualitative studies on stakeholder (HCPs, caregivers, patients) perspectives. A meta-ethnographic approach synthesized findings, with barriers/enablers classified using the theoretical domains framework (TDF). From 4319 records, 26 studies were included, yielding five key concepts: stakeholder expectations, test result significance, shared decision-making, diagnostic certainty, and test delivery systems. Barriers included lack of understanding (knowledge) and emotional burden (emotion). Enablers involved supporting decision making (memory, attention, decision processes) and beliefs about testing benefits (beliefs about consequences), though risks were equally noted. Barriers to AD biomarker use involve multiple TDF domains, with contrasting stakeholder viewpoints. Improving knowledge of biomarkers and addressing perceived benefits and risks can guide interventions, promoting more effective test use.},
}

@article {pmid42255958,
year = {2026},
author = {Trudel, L and Therriault, J and Macedo, AC and Meeker, KL and Braskie, MN and Toga, AW and Gauthier, S and Vitali, P and Schindler, SE and O'Bryant, SE and Rosa-Neto, P},
title = {Eligibility for anti-amyloid treatment in a multiethnic community-based study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70314},
pmid = {42255958},
issn = {2352-8729},
abstract = {INTRODUCTION: The approval of anti-amyloid monoclonal antibodies (mAbs), including lecanemab and donanemab, represents a significant advance in disease-modifying therapies (DMTs) for early Alzheimer's disease (AD). While appropriate use recommendations (AURs) have been established to guide clinical decision-making, the proportion of individuals with cognitive impairment in real-world, multiethnic populations meeting eligibility criteria remains unknown, as do potential differences in treatment-related risks across ethnic groups.

METHODS: We included 513 cognitively impaired individuals from the Health and Aging Brain Study-Health Disparities study, a multiethnic community-based cohort. Eligibility for lecanemab and donanemab was determined using published AUR criteria. Counts of amyloid-related imaging abnormalities were estimated based on apolipoprotein E (APOE) ε4 genotype and ethnicity using published incidence rates.

RESULTS: Only 15% of participants met eligibility criteria for lecanemab or donanemab. Black individuals had a numerically higher estimated ARIA burden, though differences were not statistically significant.

DISCUSSION: Few individuals in this community-based, multiethnic cohort met eligibility for anti-amyloid therapy, highlighting limited real-world applicability of current AURs.

HIGHLIGHTS: Only 15% of community-based individuals with MCI or dementia met eligibility criteria for lecanemab and donanemab.Black participants had numerically higher estimated ARIA cases, though not statistically significant.Current AUR criteria have limited real-world applicability across multiethnic populations.Broader inclusion criteria and real-world safety data are needed to ensure equitable, safe implementation.},
}

@article {pmid42255959,
year = {2026},
author = {Cheng, Y and Medina, A and Korponay, C and Beckmann, CF and Harper, D and Nickerson, L and , },
title = {Investigating the amyloid-tau-neurodegeneration framework in Alzheimer's disease using semi-supervised multimodal imaging data fusion.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70360},
pmid = {42255959},
issn = {2352-8729},
abstract = {INTRODUCTION: Alzheimer's disease (AD) heterogeneity complicates diagnosis and prognosis. Uncovering amyloid-tau-neurodegeneration (A-T-N) patterns may improve diagnostic prediction.

METHODS: We applied SuperBigFLICA (SBF), a semi-supervised multimodal fusion method, to gray matter density, cortical thickness (CT), pial surface area, amyloid and tau positron emission tomography maps from 274 Alzheimer's Disease Neuroimaging Initiative 3 participants to derive 50 latent components predictive of cognitive decline. Subject loadings were then used to predict diagnosis (cognitively normal, mild cognitive impairment, dementia) and apolipoprotein E (APOE) ε4 status via least absolute shrinkage and selection operator logistic regression, compared to demographic, single-modality, and naïve fusion comparator models.

RESULTS: SBF modestly predicted out-of-sample concurrent clinical severity (Clinical Dementia Rating Sum of Boxes; r = 0.21), yet models using SBF-derived loadings were among the strongest comparator models (area under the receiver operating characteristic curve; = 0.80 for diagnosis; 0.83 for APOE ε4). Amyloid alterations in sensory areas best separated dementia, while a tri-modal tau-neurodegeneration pattern related to disease progression. Loadings were validated through cerebrospinal fluid correlations.

DISCUSSION: SBF improves prediction and reveals interpretable patterns that better classify clinical diagnoses and APOE ε4 than traditional approaches.},
}

@article {pmid42255960,
year = {2026},
author = {Kodama, L and Valocchi, E and Chanfreau-Coffinier, C and Merritt, VC},
title = {Mid- and late-life depression increases risk of Alzheimer's disease and related dementias in veterans.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70364},
pmid = {42255960},
issn = {2352-8729},
abstract = {INTRODUCTION: Using 20-year data from the Veterans Health Administration's electronic health record, we explored associations between mid- and late-life depression with incident Alzheimer's disease and related dementias (ADRD).

METHODS: Participants included Veterans with (n = 272,739) and without (n = 435,965) depression matched on sociodemographic and healthcare utilization factors. International Classification of Diseases codes were used to define medical conditions. We performed a time-to-event analysis using Fine-Gray models with death as a competing event.

RESULTS: Depression was associated with ADRD (hazard ratio [HR] = 1.36; 95% confidence interval [CI] = 1.35-1.38), with higher risk for mid-life depression (age at index date <60: HR = 2.56; 95% CI = 2.44-2.69) compared to late-life depression (age ≥60: HR = 1.70; 95% CI = 1.67-1.72). This association persisted regardless of traumatic brain injury (TBI) and posttraumatic stress disorder status, but was especially strong for those with TBI prior to depression diagnosis.

DISCUSSION: Findings emphasize the need to screen for cognitive changes in Veterans diagnosed with depression, especially those with mid-life depression.},
}

@article {pmid42255961,
year = {2026},
author = {Teijeira-Portas, S and Murueta-Goyena, A and Zamora-Otaola, A and Perez, R and Fernandez, M and Almeida, J and Blanco, E and Gonzalez, T and Barrenechea, M and Ayala, U and Zuazo, G and Gomez-Esteban, JC and Acera, M and Del Pino, R and Gabilondo, I},
title = {A fovea-centered retinal signature linked to plasma biomarkers in prodromal Alzheimer's disease.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70369},
pmid = {42255961},
issn = {2352-8729},
abstract = {INTRODUCTION: Blood biomarkers detect Alzheimer's disease (AD), but tissue correlates of early tau pathology and glial activation remain unclear. We investigated whether multimodal retinal measures capture a focal prodromal AD (pAD) pattern linked to plasma biomarkers.

METHODS: Thirty-eight individuals with pAD and 40 controls underwent optical coherence tomography (OCT), OCT-angiography (OCT-A), and electroretinography (ERG). Plasma p-tau217, p-tau181, glial fibrillary acidic protein (GFAP) Aβ42 and Aβ40 were quantified, adjusting for age, sex, and vascular risk factors.

RESULTS: Between-group differences were restricted to parafoveal OCT-A measures. Within the pAD group, higher p-tau217/Aβ42 and GFAP showed consistent associations with foveal measures: increased ganglion cell-inner plexiform layer (GCIPL) thickness, capillary density, altered foveal avascular zone (FAZ), and reduced photopic negative-response amplitude. These associations were absent in controls. Mediation analyses indicated that foveal GCIPL thickness largely accounted for blood biomarker-microvascular/ERG associations.

DISCUSSION: pAD exhibits a spatially consistent, fovea-centered neurovascular and functional signature-tracking plasma tau phosphorylation and glial activation, supporting the fovea as a sensitive region in early disease-related processes.},
}

@article {pmid42255963,
year = {2026},
author = {Yamada, K and Kurihara, M and Akitomi, Y and Sato, K and Shimasaki, R and Hatano, K and Bannai, T and Suzuki, F and Furuta, K and Tokumaru, AM and Ishii, K and Ihara, R and Iwata, A},
title = {Clinical and MRI features associated with amyloid positivity in secondary screening for anti-amyloid-β therapy.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70374},
pmid = {42255963},
issn = {2352-8729},
abstract = {INTRODUCTION: In Japan, confirmatory biomarker testing for Alzheimer's disease (AD) is insurance-covered only when evaluating eligibility for anti-amyloid-β therapies. This study aimed to identify clinical and magnetic resonance imaging (MRI) features associated with amyloid positivity in a real-world setting.

METHODS: We reviewed patients attending our secondary screening clinic between 2023 and 2024. After clinical discussions, interested patients underwent 3T MRI and either amyloid positron emission tomography (PET) or cerebrospinal fluid biomarker testing.

RESULTS: Of the 200 patients, 147 proceeded to evaluation and 138 had biomarker results. The amyloid-positive group (n = 107) was younger and had lower Mini-Mental State Examination (MMSE) scores, despite similar symptom duration; younger age largely reflected early-onset cases. MRI indices overlapped between the groups, except for a higher medial-temporal-whole-brain atrophy ratio.

DISCUSSION: Younger age and lower MMSE scores were associated with amyloid positivity. Caution regarding referral bias for early-onset AD in real-world settings is warranted.},
}

@article {pmid42255964,
year = {2026},
author = {Rosenbloom, M and Adams, C and Allen, B and Berry, B and Camargo, C and Cooper, G and Giles, S and Leahy, C and Sabbagh, M and Sadowski, M and Schreiber, C and Schulz, PE and Soria, J and Weisman, D and Frech, F and Jones, DR},
title = {Real-world use of lecanemab: patient pathway findings from a US multicenter study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70376},
pmid = {42255964},
issn = {2352-8729},
abstract = {INTRODUCTION: To ensure Alzheimer's disease-modifying treatments can be initiated in diverse populations, efficient pathways to obtain timely diagnoses are required.

METHODS: This interim sub-analysis of a multicenter US study included cross-sectional surveys and interviews with neurologists at 12 diverse sites to assess real-world lecanemab use.

RESULTS: At survey completion, ∼1342 patients had received lecanemab. Most referrals originated from primary care. Amyloid pathology was confirmed primarily by positron emission tomography (58%) or cerebrospinal fluid (35%), with blood-based biomarkers (BBMs) increasingly used to reduce diagnostic delays. All sites performed apolipoprotein E4 (APOE ε4) testing to inform risk/benefit decisions. Infusions usually started within 6 months of diagnosis. Delayed/incomplete referrals were identified as the most significant barrier in the current patient pathway.

DISCUSSION: These findings demonstrate the feasibility of lecanemab integration in diverse clinical settings and highlight the importance of primary care physician engagement, optimization of referral pathways, and expanding BBM use in improving timely diagnosis, equitable access, and early treatment initiation.},
}

@article {pmid42255965,
year = {2026},
author = {Ye, W and Zhang, Z and Ye, S and Li, S and Zheng, W and Oparinde, JG and Ji, G and Linnebacher, M and Lu, L},
title = {Association between Alzheimer's/Parkinson's diseases and cancers: Modifying effects of alcohol consumption and viral infections revealed by an ecological study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70350},
pmid = {42255965},
issn = {2352-8729},
abstract = {INTRODUCTION: An inverse epidemiological association exists between Alzheimer's and Parkinson's diseases (AD/PD) and certain cancers. Using a sex-stratified approach, this global study clarifies shared and distinct mechanisms underlying the complex AD/PD-cancer relationship.

METHODS: Data from two World Health Organization (WHO) databases were analyzed for correlations between AD/PD and 23 major cancers, stratified by sex, region, and etiology.

RESULTS: An inverse association was observed between AD/PD and most, especially gastrointestinal (GI), cancers. Conversely, virus-related cancers including human papilloma virus (HPV)-driven cervical and hepatitis B virus (HBV)/hepatitis C virus (HCV)-related liver cancer (LC) were positively associated solely with PD, but not with AD. Sex-specific analyses revealed distinct patterns: oesophagus cancer (OC) was positively correlated with AD/PD only in women. LC etiology showed opposing links to PD: HBV/HCV-related positive and alcohol-related inverse. Further analysis indicated alcohol exhibited contrasting roles: positive with GI cancers but inverse with AD/PD.

DISCUSSION: We provide novel epidemiological evidence on the complex interplay between neurodegeneration and cancers, suggesting shared biological pathways and modulators.},
}

@article {pmid42255966,
year = {2026},
author = {Li, Y and Zhao, Y and Yang, A and Wang, Y and Xin, J and Chen, Y and Xing, X and Liu, F and Zou, Y and Zhao, W and Song, L and Gong, T and Wang, G},
title = {Lecanemab treatment modulates brain volume and cerebrospinal fluid pathways in early Alzheimer's disease: Insights from longitudinal magnetic resonance imaging.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70348},
pmid = {42255966},
issn = {2352-8729},
abstract = {INTRODUCTION: Lecanemab provides clinical benefits in early Alzheimer's disease (AD), but its longitudinal effects on brain structure, particularly cerebrospinal fluid (CSF) compartments, remain unclear. This study examined treatment-associated structural changes using longitudinal MRI.

METHODS: Thirty-one patients with mild cognitive impairment (MCI) or early AD underwent baseline and follow-up (1-7 months) 3D T1-weighted MRI during lecanemab treatment. Gray matter (GM), ventricular, choroid plexus (CP), and perivascular space (PVS) volumes were quantified. Longitudinal changes were analyzed with paired tests and linear mixed-effects models (LMMs).

RESULTS: Significant GM volume reductions were observed in AD-vulnerable regions (hippocampus, entorhinal cortex, precuneus), with increased CSF volumes. PVS volume showed a modest, non-significant decline. CP enlargement was associated with ventricular expansion.

DISCUSSION: Lecanemab treatment was associated with coordinated parenchymal and CSF-related structural changes. CP and PVS dynamics may represent potential MRI-based markers for monitoring early AD.},
}

@article {pmid42255968,
year = {2026},
author = {Esteller-Gauxax, D and Guillén, N and Falgàs, N and Bosch, B and Tort-Merino, A and Borrego-Écija, S and Puey, R and Ruiz-Garcia, R and Naranjo, L and Niñerola-Baizán, A and Perissinotti, A and Bargalló, N and Antonell, A and Lladó, A and Sánchez-Valle, R and Pérez-Millan, A and Balasa, M and , },
title = {Atrophy signature for alpha-synuclein copathology in Alzheimer's disease.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {2},
pages = {e70347},
pmid = {42255968},
issn = {2352-8729},
abstract = {INTRODUCTION: Brain atrophy patterns in Alzheimer's disease (AD) are well established, however, the contribution of alpha-synuclein (α-syn) copathology to these patterns remains unclear. This study investigates magnetic resonance imaging (MRI) -based atrophy patterns in AD patients with α-syn copathology.

METHODS: We study two independent cohorts: Hospital Clinic Barcelona (N = 139) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 191). Participants were classified into AD-α-syn seed amplification assay positive (αSAA+), AD-αSAA-, and healthy controls (CTR). Group comparisons of MRI regions were conducted using permutation tests adjusting for age and sex.

RESULTS: Compared to CTR, both AD-αSAA- and AD-αSAA+ showed widespread cortical thinning. Direct comparison of AD-αSAA+ versus AD-αSAA- revealed differential involvement of insular, entorhinal, lateral temporal, pre and postcentral gyrus, frontal cortices, and amygdala, although with minimum size effect.

DISCUSSION: α-Syn copathology was associated with more extensive and pronounced atrophy, especially in frontal, lateral temporal, entorhinal, and amygdalar regions. This suggests that α-syn is associated with greater neurodegeneration beyond typical AD patterns.},
}

@article {pmid42256064,
year = {2026},
author = {Wang, Y and Quan, Y and Zhou, S and Zhou, Y},
title = {Tunable acoustic rotation for deep biophysical phenotyping of preclinical Alzheimer's disease.},
journal = {Materials today. Bio},
volume = {38},
number = {},
pages = {103306},
pmid = {42256064},
issn = {2590-0064},
abstract = {Despite advances in imaging and biomarker-based approaches, early diagnosis of Alzheimer's disease (AD) at single-cell resolution remains challenging. Biophysical signals at single-cell scale such as calcium dysregulation and reduced membrane fluidity may serve as early markers of AD, yet these weak signals are difficult to capture. Here, we characterized both phenomena using sensitive optical readouts that were enhanced by acoustic-induced cell rotation. The photobleaching half-life of the calcium indicator fluorescence signal and the half-recovery time of the readout used to characterize membrane fluidity both varied with the acoustic frequency used to induce cell rotation. Signal enhancement peaked within an intermediate acoustic-frequency window and decreased at both lower and higher frequencies, producing a bandpass-like response. This frequency-dependent behavior guided the selection of optimal operating frequencies for subsequent measurements. We then established an Amyloid-β (Aβ)-induced in vitro cellular model and used multidimensional spatial, temporal, and frequency-domain features to evaluate Aβ-induced cellular stress states. The acoustic-rotation approach distinguished early Aβ-induced cellular stress from untreated controls with 99.0% accuracy and classified five cellular states defined by Aβ exposure duration with 94.8% accuracy. By actively enhancing weak single-cell functional signals, this frequency-dependent acoustic strategy provides a generalizable approach for live-cell optical phenotyping and may support future preclinical studies of AD-related cellular stress.},
}

@article {pmid42256560,
year = {2026},
author = {Bednorz, A and Religa, D},
title = {The relationship between personality traits and Alzheimer's disease: a narrative review.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1757617},
pmid = {42256560},
issn = {1664-2295},
abstract = {The relationship between personality traits and Alzheimer's disease (AD) has received increasing attention in recent research. A narrative literature search was conducted in PubMed (2014-2025) using predefined keywords, with studies selected based on relevance and methodological quality. Personality traits-particularly high neuroticism and low conscientiousness-have been consistently associated with an increased risk of AD, influencing both its onset and clinical progression. Neuroticism emerges as the most robust and consistent risk factor, linked to accelerated cognitive decline, increased risk of mild cognitive impairment (MCI), and dementia through biological, psychological, and behavioral pathways. In contrast, conscientiousness appears to exert a protective effect, being associated with reduced risk of cognitive decline and greater cognitive resilience, likely mediated by health-related behaviors and neurobiological mechanisms. Extraversion and openness show more variable and context-dependent associations, with some evidence suggesting protective roles through social engagement and cognitive reserve, whereas agreeableness demonstrates weak and inconsistent relationships with AD risk. Longitudinal studies provide the strongest evidence, indicating that personality traits act as premorbid risk or protective factors rather than solely reflecting disease-related changes, while cross-sectional findings primarily capture the clinical phenotype of AD. Overall, personality traits contribute to individual differences in vulnerability to cognitive decline, highlighting their potential utility in early risk identification and prevention strategies.},
}

@article {pmid42256567,
year = {2026},
author = {Rus Prelog, P and Zupan, M and Kovačič, A and Frol, S and Gregorič Kramberger, M},
title = {Amyloid-targeting treatment in Alzheimer's disease and concomitant antiplatelets: a clinical gray zone?.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1814289},
pmid = {42256567},
issn = {1664-2295},
}

@article {pmid42256581,
year = {2026},
author = {Yu, F and Wang, M},
title = {The effects of transcranial direct current stimulation on global cognitive function, visuospatial function, and executive function in patients with mild cognitive impairment and Alzheimer's disease: a meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1782579},
pmid = {42256581},
issn = {1664-2295},
abstract = {BACKGROUND: Transcranial direct current stimulation (tDCS) has shown promise in improving the cognitive function of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analyses involving tDCS have produced conflicting results.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy of tDCS in improving global cognition and specific cognitive domains in patients with AD and MCI.

METHODS: The review and analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases-PubMed, Web of Science, the Cochrane Library and Embase-were searched up to 20 August 2025. Cochrane's risk of bias assessment tools were used to evaluate the risk of bias and the methodological quality of the included studies. Statistical analyses were performed using Review Manager 5.3.

RESULTS: This meta-analysis of 13 studies (n = 616) showed that tDCS significantly improved global cognition as measured by MMSE and MoCA (SMD = 0.49). For other cognitive domains, evidence was limited: visuospatial ability (4 studies, Clock Drawing Test) showed a significant but preliminary effect (SMD = -0.75); attention (2 studies, Digit Span Test) showed a small effect (SMD = -0.33); executive function (4 studies, Trail Making Test) showed no significant effect (SMD = 0.09).

CONCLUSION: tDCS significantly improves global cognition in patients with AD and MCI. Preliminary evidence suggests possible benefits for visuospatial ability, but findings for attention and executive function remain inconclusive. Future studies should employ multi-test, domain-specific neuropsychological batteries in adequately powered trials.},
}

@article {pmid42256792,
year = {2026},
author = {Dong, Y and Bai, X and Chen, Y and Wang, J and Cui, Q and Fan, L and Li, S and Qiu, Y},
title = {Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke.},
journal = {Biochemistry and biophysics reports},
volume = {46},
number = {},
pages = {102654},
pmid = {42256792},
issn = {2405-5808},
abstract = {Hemorrhagic transformation (HT) is a major complication of reperfusion therapy after ischemic stroke, but its impact on Alzheimer disease (AD) progression remains unclear. In this study, we used an early-stage APP/PS1 mouse model and found that HT following transient middle cerebral artery occlusion(tMCAO) aggravated cognitive impairment and promoted AD-like pathological changes, which were markedly attenuated by Timosaponin B-II (TB-II) treatment. TB-II effectively alleviated HT following tMCAO(tMCAO/HT)-induced cognitive and recognition memory deficits in APP/PS1 mice and reduced hippocampal Aβ42 production. In vitro, TB-II pretreatment reversed oxygen-glucose deprivation/reoxygenation (OGD/R) and hemin-induced increases in Aβ42 production and apoptotic propensity, as well as decreases in mitochondrial membrane potential and cell viability in N2a/APPswe cells. Mechanistically, TB-II activated NRF2, which in turn indirectly modulating GSK-3β-mediated APP phosphorylation and negatively regulated BACE1 transcription through binding promoter binding, ultimately suppressing amyloidogenic processing. Together, our findings suggest that TB-II may serve as a potential therapeutic agent against HT-associated acceleration of AD-like pathology after ischemia-reperfusion.},
}

@article {pmid42257047,
year = {2026},
author = {Kim, TH and Kwon, JG and Chao, JS and Kim, JW and Pak, CJ and Suh, HP and Lim, JS and Hong, JP},
title = {Reply to: "Node-level inference and score construction may overstate the diagnostic utility of cervical lymph node ultrasound in Alzheimer's disease".},
journal = {Cerebral circulation - cognition and behavior},
volume = {10},
number = {},
pages = {100546},
pmid = {42257047},
issn = {2666-2450},
abstract = {•GEE sensitivity analyses retained the principal categorical findings.•Continuous nodal measurements remained non-significant after GEE adjustment.•Nested score structure reflects a phenotypic gradient, not independent signals.•AUC of single-variable model (0.770) approached that of the composite (0.808).•Composite score remains exploratory and requires external validation.},
}

@article {pmid42257358,
year = {2026},
author = {Jedidi, Z and Smeets, P and Laverdeur, J and Jedidi, H and Depierreux, F},
title = {[From Silent Spring to neuronal silence : pesticides and neurodegenerative diseases].},
journal = {Revue medicale de Liege},
volume = {81},
number = {5-6},
pages = {365-372},
pmid = {42257358},
issn = {0370-629X},
abstract = {Over sixty years ago, Silent Spring, the groundbreaking book by biologist Rachel Carson, raised global awareness of the dangers of uncontrolled pesticide use and contributed to the ban on the use of dichlorodiphenyltrichloroethane (DDT) in the USA. Many years later, it is clear that most of the issues raised in this book remain highly relevant. Today, almost our entire environment is contaminated, sometimes permanently, by pesticides. Yet the chronic toxicity of these substances is still poorly understood. In recent years, a growing body of data seems to link environmental exposure to pesticides with the risk of developing chronic neurological disorders, particularly neurodegenerative diseases. This article will attempt to present a clear and concise review of the literature on the subject, focusing on the most studied conditions, namely Parkinson's disease and Alzheimer's disease.},
}

@article {pmid42257639,
year = {2026},
author = {Kleiner, G and Lang, AE},
title = {Paratonia in Advanced Dementia: Deconstructing Scientific, Regulatory, and Health System Barriers to Botulinum Toxin A (BoNT-A) Treatment of Involuntary Muscle Resistance.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {106285},
doi = {10.1016/j.jamda.2026.106285},
pmid = {42257639},
issn = {1538-9375},
abstract = {Paratonia, a movement disorder characterized by involuntary muscle resistance, affects nearly all people with advanced dementia and contributes to caregiver burden, hygiene complications, pressure injuries, and pain. With Alzheimer's disease and related dementias affecting 7.2 million Americans and projected to reach nearly 14 million by 2060, the clinical impact of paratonia will expand proportionally. Because the involuntary muscle resistance of paratonia is frequently misinterpreted as deliberate noncompliance, individuals may receive inappropriate pharmacologic management rather than targeted treatment of the underlying movement disorder. No treatments are currently approved specifically for paratonia-induced muscle postures. Passive motion therapy, which the Centers for Medicare & Medicaid Services quality standards promote for contracture prevention in nursing homes, showed no benefit for paratonia in a randomized controlled trial of individuals with advanced dementia. Furthermore, passive movement therapy may paradoxically reinforce abnormal motor patterns by triggering increased involuntary resistance, the defining feature of paratonia. Botulinum toxin A, in therapeutic use since 1989, with Food and Drug Administration approval, is an established treatment for post-stroke spasticity and cervical dystonia. These conditions, like paratonia, arise from distinct central nervous system pathologies but share a peripheral manifestation of involuntary sustained muscle contraction. Preliminary clinical evidence suggests potential safety and efficacy for paratonia-induced muscle postures. Despite the therapeutic rationale and preliminary evidence for safety and efficacy, pharmaceutical companies have not pursued regulatory approval for the paratonia indication. This article examines barriers to clinical development, including scientific uncertainties, knowledge gaps, infrastructure limitations, therapeutic nihilism, policy barriers, and pharmaceutical industry considerations. We propose coordinated stakeholder action across research, education, policy, and regulatory domains to establish pathways toward further research and, if warranted, clinical implementation.},
}

@article {pmid42257667,
year = {2026},
author = {Silva-Silva, J and González San Martín, E},
title = {[Ethical Issues in Early Serological Diagnosis of Alzheimer's Disease].},
journal = {Revista medica de Chile},
volume = {154},
number = {3},
pages = {423-429},
doi = {10.4067/s0034-98872026000300423},
pmid = {42257667},
issn = {0717-6163},
abstract = {UNLABELLED: The ethical conflicts involved in the medical indication of early serological diagnosis in Alzheimer's disease, for clinical contexts where a medical indication is required to perform the intervention, have been scarcely analyzed.

HYPOTHESIS: The prescription of early serological diagnosis in Alzheimer's disease violates more principles than it supports.

AIM: To carry out an analysis regarding the ethical conflicts associated with the indication of early serological diagnosis of Alzheimer's disease and to offer a clinical practice recommendation based on said analysis.

METHODS: Ethical analysis, in which the logical consequences of prescribing early serological diagnosis will be explained in terms of the ethical principles of autonomy, justice, beneficence and non-maleficence.

RESULTS: The intervention presents marginal benefit in terms of autonomy and beneficence, while it violates the principles of beneficence, non-maleficence and justice.

CONCLUSIONS: The intervention is not ethically recommended. This could change if its cost diminishes and if disease-modifying therapies with an adequate safety profile are developed.},
}

@article {pmid42257730,
year = {2026},
author = {Gupta, A and Chawla, S},
title = {Digital Resources for Traversing the Landscape of Human Aging: Databases, Key Computational Strategies, and Artificial Intelligence.},
journal = {Omics : a journal of integrative biology},
volume = {},
number = {},
pages = {15578100261457662},
doi = {10.1177/15578100261457662},
pmid = {42257730},
issn = {1557-8100},
abstract = {By 2050, nearly 20% of the global population will exceed 60 years old, experiencing compromised physiological and functional abilities, neurological disorders, and sarcopenia. Geroscience has evolved immensely through OMICS approaches and high-throughput technologies, generating massive datasets requiring efficient management, annotation, and storage. This highlights the need for user-friendly databases integrated with machine learning (ML) and artificial intelligence (AI). This review provides a comparative synthesis of the state-of-the-art databases on longevity genes, age-related signaling pathways, model organism phenotypes, and manually curated aging/antiaging experimental studies. We delineate the architecture, methodology, and functional features of contemporary geroscience databases, detailing the objectives, content, and dataset size, including multiomics information. Critically, these databases facilitate geriatric interventions: from biomarker discovery to drug repositioning, significantly impacting aging-associated conditions like muscle loss and Alzheimer's. In addition, we present updated insights into the increasing use of deep aging clocks and multiomics databases, coupled with ML- and AI-dependent analyses, fostering advanced dataset development. Interestingly, these tools are capable of dataset pattern recognition, predictive modeling, and the generation of research hypotheses. By bridging manually curated and AI-driven tools, this review offers a holistic view of the complementary strengths of aging databases, paving the way for the next generation of geroscience.},
}

@article {pmid42257810,
year = {2026},
author = {Sivalingam, AM},
title = {DJ-1 in the Neuro-cutaneous Aging Axis: Unifying Pathways of Parkinson's Disease Neurodegeneration, Progression, and Redox-Based Therapeutic Strategies for Healthy Longevity.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42257810},
issn = {1559-1182},
abstract = {Sleep and circadian disturbances precede motor symptoms in Parkinson's disease (PD), acting as early neurodegeneration indicators. Disrupted rhythms, mitochondrial dysfunction, neuroinflammation, and neurotransmitter imbalance create a self-reinforcing cycle that accelerates progression. DJ-1 (PARK7), a redox-sensitive protein, provides central neuroprotection by preserving mitochondrial integrity, mitigating oxidative stress, and curbing neuroinflammation. DJ-1 loss or mutation weakens antioxidant defences, promotes α-synuclein aggregation, and worsens dopaminergic neuron loss, positioning it as a key biomarker and therapeutic target. Oxidative stress, mitochondrial impairment, chronic inflammation, and telomere attrition link neurodegeneration to systemic and skin aging via a "neuro-cutaneous aging axis." Similar mechanisms include mitochondrial dysfunction, ferroptosis, and redox imbalance energy Alzheimer's cognitive decline. Chronotherapy, NRF2 activators, phytochemicals, nanozymes, and postbiotics offer promise in restoring redox balance and halting progression. Telomere dysfunction and genomic instability further connect neural and skin aging, modulated by environment, diet, and lifestyle. Micro physiological systems, predictive analytics, and personalized medicine enhance mechanistic insights and therapy development. Targeting interconnected pathways of redox regulation, mitochondrial function, proteostasis, and telomere maintenance provides a unified approach to combat neurodegeneration and aging. DJ-1-focused therapies, paired with antioxidants and mitochondrial interventions, hold strong potential for disease modification and healthy aging.},
}

@article {pmid42258028,
year = {2026},
author = {Alotaibi, MO and Al-Kuraishy, HM and Fahad, EH and Abdelaziz, AM and El-Saber Batiha, G},
title = {Targeting inflammaging in Alzheimer's disease: molecular pathways and emerging pharmacotherapies.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42258028},
issn = {1568-5608},
abstract = {Alzheimer's disease (AD), the leading cause of dementia, is intrinsically linked to the aging process. A central mechanism driving this association is inflammaging, a state of chronic, low-grade inflammation resulting from innate immune dysregulation. Emerging evidence suggests that inflammaging is not merely a background feature of aging but an active pathogenic driver of AD, accelerating amyloid-β accumulation, tau hyperphosphorylation, and synaptic failure. This review synthesizes the molecular circuitry connecting inflammaging to AD, detailing the synergistic roles of the NLRP3 inflammasome, impaired autophagy, TREM2 signaling, and the cGAS-STING pathway. Furthermore, we critically evaluate pharmacological strategies designed to disrupt these cascades, including specific NLRP3 inhibitors, senolytic agents, and autophagy enhancers. We propose that these therapies offer a vital complementary approach to amyloid-targeting treatments, potentially modifying disease progression by extinguishing the persistent inflammatory milieu of the aging brain.},
}

@article {pmid42258102,
year = {2026},
author = {Otomi, Y and Shinya, T and Otsuka, H and Kamei, Y and Badarchin, M and Matsushita, T and Takaoka, Y and Hiroshima, Y and Matsubara, T and Fujita, K and Tomioka, Y and Nakataki, M and Numata, S and Izumi, Y and Harada, M},
title = {Quantitative agreement between AMYclz and CortexID for [18]F-florbetapir amyloid PET: a retrospective study of 103 patients.},
journal = {Japanese journal of radiology},
volume = {},
number = {},
pages = {},
pmid = {42258102},
issn = {1867-108X},
support = {JP24K15767//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: Quantitative analysis of amyloid PET images is increasingly used to support visual interpretation and to provide objective measures of amyloid burden. However, quantitative values may vary depending on the analysis software used. This study aimed to evaluate the quantitative agreement between two analysis platforms, AMYclz and CortexID, for [18]F-florbetapir amyloid PET.

MATERIALS AND METHODS: This retrospective study included 103 consecutive patients who underwent [18]F-florbetapir PET for evaluation of cognitive impairment. Visual interpretation was used to classify scans as amyloid-positive or amyloid-negative. Quantitative analysis was performed using CortexID and AMYclz software to obtain global cortical standardized uptake value ratios (SUVr). AMYclz additionally provided Centiloid scale (CL) values. The ability of quantitative metrics to differentiate visually positive and negative scans was evaluated using receiver operating characteristic (ROC) analysis, and agreement between software platforms was assessed using correlation, linear regression, and Bland-Altman analysis.

RESULTS: Among 103 patients, 59 were visually classified as amyloid-positive and 44 as amyloid-negative. CortexID SUVr values were significantly higher in amyloid-positive patients than in amyloid-negative patients (1.30 ± 0.14 vs. 0.97 ± 0.09, p < 0.001). AMYclz SUVr showed similar separation between groups (1.34 ± 0.14 vs. 0.99 ± 0.09, p < 0.001). ROC analysis demonstrated excellent discrimination for CortexID SUVr (AUC = 0.986), AMYclz SUVr (AUC = 0.996), and CL values (AUC = 0.996). CortexID and AMYclz SUVr values showed strong correlation (r = 0.957) with minimal systematic bias. Discordant classification between the two software platforms was observed in three cases (2.9%), all near the diagnostic threshold.

CONCLUSION: AMYclz and CortexID demonstrated excellent quantitative agreement for [18]F-florbetapir amyloid PET. Both AMYclz SUVr and CL values showed excellent ability to differentiate visually amyloid-positive and amyloid-negative scans, supporting the reliability of quantitative amyloid PET analysis across different software platforms in clinical practice.},
}