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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41608511,
year = {2025},
author = {Xu, Y and Gao, J and Wang, M and Zhang, H},
title = {Exercise-mimicking effects of betaine in chronic disease prevention and management.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1762908},
pmid = {41608511},
issn = {2296-861X},
abstract = {Betaine, a natural compound found in beets, wheat germ, shellfish, and mammalian tissues, plays a crucial role in preventing and treating various chronic diseases. As the global population ages, chronic diseases are posing the primary threat to the health of the elderly, significantly increasing the medical pressure on families and society. Chronic diseases associated with aging involve complex molecular mechanisms and, therefore, developing multipronged interventions is crucial for their prevention and treatment. Although exercise is a primary intervention for preventing and treating chronic diseases, many elderly individuals have motor disabilities. Therefore, researchers are exploring natural products that mimic the therapeutic effects of exercise in individuals who are unable to exercise. Betaine has exhibited significant preventive and therapeutic effects in studies on chronic diseases and is known as an exercise mimetic. A deeper understanding of betaine may help elucidate crucial molecular mechanisms underlying its effects and offer theoretical insights for developing exercise-mimicking foods, supplements, and drugs, which are expected to benefit the human health.},
}

@article {pmid41608480,
year = {2025},
author = {Robinson, M and Picco, L and Payton, OD and Zelem, N and Baur, C and Beazely, MA and Miles, MJ and Leonenko, Z},
title = {Dynamic instability in nanoscale lipid domains revealed by contact mode high speed AFM: effect of amyloid-β and cholesterol content.},
journal = {Nanoscale advances},
volume = {},
number = {},
pages = {},
pmid = {41608480},
issn = {2516-0230},
abstract = {Cellular membranes are an essential feature of life, the composition and structure of which is important in governing cellular processes and is linked to multiple disorders. Of particular interest is the role that the lipid membrane plays in amyloidogenic diseases such as Alzheimer's disease (AD), including the role of lipid composition and cholesterol in mediating amyloid toxicity. To mimic neuronal membranes, we used 3-component (DPPC/DOPC/Chol) and 5-component (DPPC/POPC/Chol/sphingomyelin/GM1) model membranes. Atomic force microscopy (AFM) is a key tool in studying the structures of lipid membranes and their interactions with amyloid. Recent advances in contact mode high-speed AFM (HS-AFM) have made it possible to capture dynamic processes at video rate. We used a unique custom-built contact mode HS-AFM to image model lipid membranes and study amyloid-β interactions in liquid. We demonstrate the advantage of using HS-AFM coupled with spatiotemporal variability analysis to capture the dynamic interaction of Aβ 1-42 monomers and oligomers with phase separated lipid bilayers to elucidate the role of nanoscale domains in amyloid-membrane interactions. We show that amyloid oligomer complexes induce greater dynamic instability than monomers, and that low cholesterol membranes are more susceptible to destabilization. Overall, we demonstrate the advantage of HS-AFM to image biological processes on biologically relevant soft samples and discuss tip-sample interactions at high-speed operation in contact mode on lipid membrane models in a liquid environment.},
}

@article {pmid41608471,
year = {2025},
author = {Rao, JS and Alejandra Tangarife, M and Venegas, MM and Forero, B and González Tamayo, LL and Escobar-Gallego, JP and Rodríguez-Soacha, DA and Ferreiros, A and Mukunda, R},
title = {The role of the endocannabinoid system in managing neuropsychiatric symptoms in Alzheimer's disease.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1709266},
pmid = {41608471},
issn = {1664-0640},
abstract = {The endocannabinoid system comprises cannabinoid receptors (CBRs) 1 & 2, endocannabinoids (eCBs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and the enzymes that regulate their production and degradation. ECS plays a significant role in both health and disease. It influences neuronal and glial communications, neurotransmitter regulations, neuroinflammation, and behavioral alterations. Neuropsychiatric symptoms (NPS) are commonly seen in neurodegenerative conditions like Alzheimer's disease (AD), apart from the core clinical diagnosis of dementia. NPS consists of various disturbing symptoms, including anxiety, agitation, apathy, hallucinations, delusions, sleeping problems, appetite problems, and depression. In AD, up to 97% exhibit one or more NPS. Emerging evidence from preclinical and clinical studies suggests that ECS is both a contributor to and a potential therapeutic target for managing NPS. This review explores ECS's role in NPS and its therapeutic implications.},
}

@article {pmid41608351,
year = {2025},
author = {Bednorz, A and Trybek, P and Hoang, MT and Religa, D},
title = {Sex differences in APOE- and PICALM-related cognitive profiles in healthy middle-aged adults.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1694701},
pmid = {41608351},
issn = {2673-6217},
abstract = {INTRODUCTION: The APOE ε 4 and PICALM GG genotypes are strong genetic risk factors for Alzheimer's disease. This study aimed to identify cognitive subgroups using unsupervised machine learning and to investigate the influence of APOE and PICALM genotypes on cognitive performance.

MATERIAL AND METHODS: Cognitive, genetic and demographic data from 192 healthy middle-aged adults (50-63 years) from the PEARL-Neuro Database were analyzed using agglomerative hierarchical clustering. Neuropsychological tests included the California Verbal Learning Test, Raven's Progressive Matrices, and the Edinburgh Handedness Inventory. Subsequent analyses used linear regression models to assess the effects of APOE, PICALM, and their interaction on cognitive outcomes.

RESULTS: Two cognitive subgroups (better vs. worse performance) were identified for both females (n = 60/43) and males (n = 38/51). In women with lower cognitive performance, the presence of the APOE ε 3 ε 4 allele was significantly associated with a higher number of perseverations (CVLT9: p FDR = 0.02 , R 2 = 0.18) and lower recognition accuracy (CVLT12: p FDR = 0.04 , R 2 = 0.12). A significant PICALM GG × education interaction was observed for fluid intelligence (p FDR = 0.03 , R 2 = 0.34). In men with lower cognitive performance, the APOE ε 3 ε 4 genotype was associated with lower fluid intelligence scores (RPM: p FDR = 0.04 , R 2 = 0.09). Furthermore, significant APOE × PICALM interactions were found for verbal learning (CVLT1: p FDR = 0.03 , R 2 = 0.16) as well as delayed cued recall (CVLT6: p FDR = 0.03 , R 2 = 0.12 ; CVLT8: p FDR = 0.03 , R 2 = 0.13).

CONCLUSION: This study revealed significant sex differences in gene-cognition interactions. In females with lower cognitive performance, the genotype APOE ε 3 ε 4 was associated with poorer recognition, while the combined effects of APOE × PICALM in males were associated with weaker episodic memory. Although performance remained within normative ranges, these subtle differences may indicate early risk and warrant longitudinal monitoring.},
}

@article {pmid41608075,
year = {2025},
author = {Kapoor, A and Mather, M and Nation, DA},
title = {Emotional enhancement of memory in Alzheimer's disease dementia: a systematic review.},
journal = {Nature. Mental health},
volume = {3},
number = {9},
pages = {1078-1087},
pmid = {41608075},
issn = {2731-6076},
abstract = {Progressive decline in episodic memory is a hallmark of Alzheimer's disease (AD). Emotional arousal is known to enhance memory. Enhanced encoding of emotionally arousing stimuli or events may improve memory in patients with AD; however, whether this effect is present in patients with AD remains unclear. Here we conducted a systematic search of the literature to identify relevant literature on emotional enhancement of memory in AD. Inclusion criteria were studies that (1) included individuals with Alzheimer's disease and (2) assessed emotional memory, particularly episodic memory. Thirty-five studies were included. Twelve out of 35 studies (34.3%) showed clear emotional enhancement of memory for episodic memory among participants with mild AD, while 13 studies (37.1%) found no effect. Ten studies (28.6%) found that emotional enhancement of memory was influenced by stimuli type, valence of emotion, level of encoding or intensity of emotion. Studies including brain imaging showed that amygdala and hippocampus volume are strong predictors of emotional enhancement of memory in AD, regardless of level of cognitive impairment. Evaluating volumes or networks of brain regions known to be involved in emotional memory processing may be a key factor influencing the preservation of enhanced encoding of emotional information. Future studies are needed to confirm whether atrophy of memory-related brain regions diminishes emotional enhancement of memory in AD.},
}

@article {pmid41607889,
year = {2025},
author = {Zhang, Y and Xu, W},
title = {Accelerometer-based physical activity, air pollution and risk of dementia subtypes: a prospective study using UK biobank.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1695462},
pmid = {41607889},
issn = {2296-2565},
mesh = {Humans ; *Air Pollution/adverse effects/statistics & numerical data/analysis ; *Exercise/physiology ; Male ; United Kingdom/epidemiology ; Female ; *Accelerometry ; Prospective Studies ; *Dementia/epidemiology ; Aged ; Middle Aged ; Particulate Matter/analysis ; Air Pollutants/analysis/adverse effects ; Risk Factors ; Biological Specimen Banks ; Proportional Hazards Models ; Alzheimer Disease/epidemiology ; UK Biobank ; },
abstract = {BACKGROUND: The protective effect of physical activity on dementia risk is well established, yet the magnitude of effect remains highly inconsistent, possibly due to various approaches to physical activity measurement and potential moderating effects of environmental factors such as air pollution.

OBJECTIVE: To evaluate the independent and interaction effects of air pollution and accelerometer-based physical activity on incident risks of dementia subtypes.

METHODS: This study included 96,661 participants from the UK Biobank study with accelerometer-derived physical activity measures. Dementia diagnosis was algorithmically defined based on self-reports, primary care, hospital, and mortality records. We assessed five air pollutants, including particulate matters (PM2.5, PM2.5-10, PM10), nitrogen dioxide (NO2), and nitrous oxides (NOx). Multivariable-adjusted Cox proportional hazard models were employed to estimate the associations between physical activity, air pollution, and the risks of Alzheimer's Disease (AD) and Vascular Dementia (VaD). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Several sensitivity analyses were conducted to assess the robustness of the results.

RESULTS: A one-IQR (10.13 milli-gravity) higher level of physical activity was significantly associated with a 30% lower risk of AD (HR = 0.7, 95% CI: 0.57-0.86, p < 0.001) and a 32% lower risk of VaD (HR = 0.68, 95% CI: 0.5-0.91, p < 0.05). Exposure to NO2 was significantly associated with an increased incident risk of AD, while exposure to PM2.5, PM2.5-10, PM10, and NO2 was associated with an increased risk of VaD. Results from models with interaction terms indicate that the protective effect of physical activity against AD was attenuated among individuals exposed to higher levels of PM2.5 and NO2, and that the effect of physical activity against VaD was attenuated by higher PM2.5-10 exposure.

SIGNIFICANCE: This study provides new evidence on the independent and interactive effects of objectively measured physical activity and air pollution on the risks of dementia subtypes, thereby improving the biological specificity of these associations.},
}

Humans
*Air Pollution/adverse effects/statistics & numerical data/analysis
*Exercise/physiology
Male
United Kingdom/epidemiology
Female
*Accelerometry
Prospective Studies
*Dementia/epidemiology
Aged
Middle Aged
Particulate Matter/analysis
Air Pollutants/analysis/adverse effects
Risk Factors
Biological Specimen Banks
Proportional Hazards Models
Alzheimer Disease/epidemiology
UK Biobank

@article {pmid41607671,
year = {2025},
author = {Tommet, D and Foldi, NS and Lamar, M and Wang, C and Rabin, L and Grandoit, E and Choi, SE and Jutten, RJ and Lee, M and Nakano, C and Gibbons, LE and Scollard, P and Mungas, D and Jones, RN and , and Crane, PK},
title = {Six month repeat cognitive testing to identify people with MCI at greatest AD dementia risk.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.30.25343228},
pmid = {41607671},
abstract = {INTRODUCTION: People with mild cognitive impairment (MCI) are candidates for early intervention, but not all progress to Alzheimer's disease (AD) dementia. Identifying a subgroup at highest risk may improve treatment targeting.

METHODS: We analyzed data from participants with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive domains included memory, executive functioning, language, and visuospatial abilities. We evaluated baseline performance and 6-month change scores, using proportional hazards models to estimate associations with time to conversion to AD dementia.

RESULTS: The strength of association varied by domain, but in general both baseline performance and 6-month change were associated with conversion. The strongest effects observed for memory and language. Observed associations were largely independent of established risk biomarkers, including APOE genotype, structural MRI measures, and CSF biomarkers.

DISCUSSION: 6-month change scores on cognitive tests may help identify a high-risk subgroup of persons with MCI likely to progress to AD dementia.

RESEARCH IN CONTEXT: Systematic review. The authors reviewed the literature using traditional (e.g. PubMed) sources. There is a modest literature on change scores in the context of the AD clinical spectrum, but few investigations have evaluated whether short-term changes may be able to identify a high-risk subgroup of people with MCI. The authors have published a systematic review of this literature (Jutten et al. 2020) and appropriately refer to relevant citations here.Interpretation: Our findings suggest that short-term changes in cognition may be useful as part of a strategy to identify subsets of people with MCI who are at highest risk of conversion. Findings were clearest for memory and language. Domain-specific changes appeared to be independent from other biomarkers used to identify people at highest risk. Domain-specific changes did not appear to be better than changes in global cognition as measured by the MMSE or the CDR-sum of boxes.Future directions: Short-term changes in cognition may be useful to help identify a subgroup of people with MCI at highest risk of conversion to AD dementia. Future work could consider time frames shorter than the 6-month data we had available, better characterizing changes with more than 2 time points, or developing strategies that combine changes in cognition with other biomarkers to identify a subgroup of people with MCI to target for treatment.},
}

@article {pmid41607663,
year = {2025},
author = {Faul, JD and Collins, S and Smith, T and Klopack, ET and Mitchell, C and Crimmins, EM and Farina, MP},
title = {Epigenetic g predicts cognitive aging and incident dementia in a diverse, nationally representative sample of older adults.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.23.25342931},
pmid = {41607663},
abstract = {BACKGROUND: Alzheimer's disease and related dementias (ADRD) are major public health concerns. DNA methylation (DNAm)-based biomarkers such as GrimAge and PhenoAge predict aging and health risk, but were not designed to optimize prediction of cognitive decline. Epigenetic g -a DNAm-derived index of general cognitive ability-is a promising marker of cognitive function that has not been assessed in a racially and socioeconomically diverse population.

METHODS: We used data from the 2016 Venous Blood Study of the Health and Retirement Study (HRS), a nationally representative cohort of U.S. adults aged ≥51 years (N = 3575 with high-quality DNAm). Epigenetic g scores were computed using CpG weights from a BayesR+ model of general cognitive ability developed in Generation Scotland. Cognitive function was measured with a modified version of the Telephone Interview for Cognitive Status (TICS) at each interview wave; 6-year incident dementia was defined using the validated Langa-Weir algorithm. Linear regression estimated associations with cognitive scores; logistic regression estimated 4-year dementia risk. Models were adjusted sequentially for demographics, education, parental education, APOE ε4 status, and blood-based neurodegeneration markers (NfL, GFAP, Aβ42/40, pTau181).

RESULTS: Higher epigenetic g was associated with better baseline cognition (β=2.55, 95% CI 1.92-3.17) and cognition at the time DNAm was measured (β=2.30, 95% CI 1.62-2.99) after demographic adjustment. Associations attenuated but remained significant with education and parental education (β=1.23-1.89). Each unit increase in epigenetic g predicted 29% lower 6-year risk of dementia (fully adjusted HR=0.71). Results were robust to adjustment for APOE ε4 and neurodegeneration biomarkers.

CONCLUSIONS: Epigenetic g is a scalable, blood-based marker of cognitive function and dementia risk that adds predictive value beyond demographics, socioeconomic indicators, APOE, and neuropathology. Its validation in a diverse, nationally representative U.S. cohort underscores its potential for early risk profiling and for research on social determinants of cognitive aging in cross-national samples.},
}

@article {pmid41607505,
year = {2025},
author = {Pahal, S and Ganne, A and Balasubramaniam, M and Griffin, ST and Shmookler Reis, RJ and Ayyadevara, S},
title = {The aggregate proteome of Caenorhabditis elegans mitochondria implicates shared mechanisms of aging and Alzheimer's disease.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1713391},
pmid = {41607505},
issn = {1663-4365},
abstract = {BACKGROUND: Mitochondrial dysfunction and protein aggregation are central features of brain aging and Alzheimer's disease (AD). To define how AD seed proteins modulate these processes, we applied quantitative proteomics to sarkosyl-insoluble aggregates from C. elegans models of normal aging and from worms expressing human Aβ or Tau transgenes.

RESULTS: Normal aging produced a late-onset accrual of mitochondrial proteins within aggregates, implicating impaired energy metabolism and proteostasis collapse. Aβ expression caused a striking expansion and included glycolytic enzymes, tricarboxylic acid cycle components, ribosomal proteins, and trafficking factors, consistent with broad proteostatic and bioenergetic stress, largely overlapping with aging-associated species, yet advanced in onset. Tau expression yielded a smaller set enriched for cytoskeletal, vesicular, and nuclear pore components. Post-translational modifications (4-HNE adducts, phosphorylation, acetylation, methionine oxidation) revealed distinct trajectories: Aβ imposed early oxidative and phosphorylation burden, whereas Tau and aging showed midlife PTM peaks consistent with delayed proteostasis collapse. Cross-species comparison revealed 68 insoluble proteins shared between worm models and human AD brain aggregates. From these, 17 conserved metabolic, chaperone, and trafficking proteins were prioritized by network metrics and validated functionally: RNAi knockdowns aggravated paralysis or impaired chemotaxis, confirming their functional importance.

CONCLUSION: These findings place mitochondrial proteome collapse at the center of aging and AD-seeded pathology, distinguish Aβ- and Tau-driven proteotoxic routes, and nominate a conserved panel of aggregation-prone proteins as mechanistic drivers and candidate biomarkers for early detection and intervention in AD.},
}

@article {pmid41607504,
year = {2025},
author = {Huang, Z and Liu, W and Zhang, Y and Zha, B and Wang, P and Yang, J},
title = {Research trends and frontiers of astrocytes in cognitive impairment: a bibliometric analysis from 2015 to 2024.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1708008},
pmid = {41607504},
issn = {1663-4365},
abstract = {OBJECTIVE: Astrocytes, constituting the predominant glial cell population with in the central nervous system, have emerged as a focal point of investigation due to their multifaceted roles and therapeutic implications in cognitive disorders. Despite the growing body of research, there has yet to be a bibliometric analysis to determine research trends and hotspots in this field.

METHODS: We searched for publications related to cognitive impairment and astrocytes in the Web of Science Core Collection (WoSCC), PubMed, and Scopus databases from January 1, 2015, to December 31, 2024. Using VOSviewer, CiteSpace software, and bibliometrix based on the R programming language, we performed visualization and bibliometric analysis of WoSCC data, covering aspects such as countries, institutions, authors, journals, keywords, and references. Additionally, we conducted equivalent searches in the Scopus and PubMed databases using the same keyword combinations, time range, and screening criteria. By verifying the consistency of time series, thematic focus, and country rankings across databases, we ensured the stability and universality of the results.

RESULTS: Over the past decade, investigations into the role of astrocytes in cognitive disorders have demonstrated a consistent upward trajectory, with the United States and China emerging as leading contributors. The primary focus has been on Alzheimer's disease, Parkinson's disease, VD, and Traumatic brain injury. The hippocampus has been identified as a critical brain region in these studies. Neuroinflammation has persisted as a central research focus and continues to represent a key direction for future investigations. Synaptic dysfunction is a recent research hotspot. The integration of single-cell sequencing technology has facilitated more comprehensive mechanistic analyses in this field. Multi-database validation results indicate that publication trends, thematic priorities, geographical distribution, and journal distribution exhibit macro-level stability.

CONCLUSION: This study employed bibliometric methods to map the development trends and research hotspots in studies related to astrocytes and cognitive impairments over the past decade, and emphasized the importance of translating current research into clinical applications. This will provide insights and references for future studies.},
}

@article {pmid41607502,
year = {2025},
author = {Li, Y and Tan, Y and Zuo, W},
title = {Autophagy-mediated regulation of neutrophil inflammatory responses and its relevance to central nervous system diseases.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1702993},
pmid = {41607502},
issn = {1663-4365},
abstract = {Autophagy is an intracellular degradation system, which plays a crucial role in regulating the inflammatory functions of neutrophils. Neutrophils, as crucial immunological phagocytes, are integral to inflammatory responses. In central nervous system diseases, neutrophils' malfunction is closely associated with disease progression. Autophagy in neutrophils is highly conserved and plays a crucial regulatory role in both the biological functions and pathophysiological processes of neutrophils. In this review, we comprehensively explore the mechanisms of autophagy and its regulatory roles in various aspects of neutrophil biology, including the neutrophil life cycle, extracellular net traps (NETs) formation, degranulation, migration and adhesion, and phagocytosis. We also analyze the role of neutrophil autophagy in different central nervous system diseases such as Alzheimer's disease, stroke, and neuroglioma. Regulating autophagy to control neutrophil inflammatory functions may emerge as a novel therapeutic strategy for treating central nervous system disorders.},
}

@article {pmid41607501,
year = {2025},
author = {Ballotta, D and Casadio, C and Tondelli, M and Zanelli, V and Ricci, F and Carpentiero, O and Lui, F and Filippini, N and Chiari, A and Molinari, MA and Benuzzi, F},
title = {The olfactory functional network in the Alzheimer's disease continuum: a resting state fMRI study.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1744413},
pmid = {41607501},
issn = {1663-4365},
abstract = {INTRODUCTION: Olfactory dysfunction is common in the Alzheimer's Disease continuum, and olfaction may be altered before clinical syndrome onset. The present study aimed at investigating the functional connectivity of the olfactory cortex and its correlation with olfaction performance in a group of patients with Mild Cognitive Impairment (MCI) who subsequently converted or not converted to Alzheimer's Disease (AD) dementia.

METHODS: At baseline, 30 MCI patients were evaluated with the Sniffin' Sticks (threshold, discrimination, and identification) to assess olfactory capacities, and they were followed up over time to identify converter and stable patients. Resting-state fMRI data acquired at baseline were analyzed to assess functional connectivity of left and right olfactory cortex. Beta values were extracted from the stable versus converter contrasts and correlated with olfactory scores.

RESULTS: Functional connectivity of the olfactory cortex was significantly increased with the posterior cingulate cortex, and significantly decreased with middle cingulate cortex, supplementary motor area, and left pre- and postcentral gyri, in converter compared to stable patients. Reduced negative functional connectivity between olfactory cortex and left angular gyrus emerged in converter patients, and a negative correlation was found between angular gyrus and discrimination scores.

DISCUSSION: Our findings indicate alterations of functional connectivity of the olfactory cortex in subjects with MCI at risk of conversion to AD dementia, even at the early stages of the disease. Additionally, the negative correlation between olfactory ability and the angular gyrus functional connectivity, a cerebral region known to be involved in multisensory integration processing, may be considered as a marker of disease progression.},
}

@article {pmid41607407,
year = {2025},
author = {Reading, CL and Yan, J and Testa, MA and Simonson, DC and Javaid, H and Schmunk, L and Martin-Herranz, DE and Brooke, R and Gordevicius, J and Zhang, J and Yuan, H and Ahlem, C and Wang, L and Markham, P and Osman, N and O'Quinn, S and Palumbo, J},
title = {Correction: An exploratory analysis of bezisterim treatment associated with decreased biological age acceleration, and improved clinical measure and biomarker changes in mild-to-moderate probable Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1758523},
doi = {10.3389/fnins.2025.1758523},
pmid = {41607407},
issn = {1662-4548},
abstract = {[This corrects the article DOI: 10.3389/fnins.2025.1516746.].},
}

@article {pmid41607405,
year = {2025},
author = {Crivelli, SM and Quadri, Z and van Kruining, D and Martinez-Martinez, P and Bieberich, E and Chatton, JY},
title = {Editorial: The role of glial cells in the pathophysiology and treatment of Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1749170},
doi = {10.3389/fnins.2025.1749170},
pmid = {41607405},
issn = {1662-4548},
}

@article {pmid41607403,
year = {2025},
author = {Zhao, M and Jiang, J and Wang, L and Yang, S and Li, W and Ren, Q and Zhang, H and Jiang, T and Jiang, S and Zhou, J and Xu, J},
title = {Longitudinal trajectories of cognitive decline and temporal lobe atrophy based on baseline gonadotropins and testosterone.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1696274},
pmid = {41607403},
issn = {1662-4548},
abstract = {INTRODUCTION: Although previous studies have reported associations between gonadotropins, testosterone, and Alzheimer's disease (AD), their longitudinal relationships with cognitive decline and temporal lobe atrophy remain insufficiently characterized. This study examined the association between baseline hormone levels and cognitive decline and temporal lobe volume loss trajectories, and whether these associations vary by sex or APOEε4 status.

METHODS: This study included 490 participants (378 MCI/112 AD; 311 men/179 women; mean age = 75.01 ± 7.52) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Baseline plasma levels of gonadotropins (FSH, LH) and total testosterone (TT) were measured using Luminex xMAP multiplex immunoassay. Cognitive decline was assessed longitudinally through MMSE and ADAS-Cog 13 scores. Temporal lobe atrophy was quantified using tensor-based morphometry of 1.5T MRI scans, with bilateral temporal lobe volumes scaled to a normalized reference (1,000 = baseline). Linear mixed effects models were employed to relate baseline plasma hormones to longitudinal cognitive performance and temporal lobe volume.

RESULTS: Longitudinal analyses showed that higher baseline FSH levels were associated with faster cognitive decline (MMSE: β = -0.025, P = 0.012; ADAS-cog: β = 0.066, P = 0.020) and accelerated temporal lobe atrophy (β = -0.115, P = 0.005) in fully adjusted models. LH was also associated with faster temporal lobe atrophy (β = -0.077, P = 0.034), while TT showed no significant association. Sex-stratified analyses showed that higher TT was associated with slower MMSE decline in women (β = 0.022, P = 0.032) but not in men (P = 0.762), with a significant sex interaction (P-interaction = 0.020). Modification effects of APOEε4 status on cognition and temporal lobe volume changes were not observed for FSH, LH, or TT.

DISCUSSION: The results indicate that in individuals across the AD spectrum, elevated gonadotropin levels may exert deleterious, domain-specific effects on cognitive decline or temporal lobe atrophy. Women with lower TT levels may experience faster cognitive progression. Although future studies incorporating additional longitudinal hormone measurements and cognitive trajectories are warranted, our results underscore the importance of gonadotropins and testosterone in AD progression.},
}

@article {pmid41607364,
year = {2026},
author = {Riedel, CS and Milan, JB and Jørgensen, NR and Jennum, P and Juhler, M},
title = {Overnight Dynamics of Ventricular Cerebrospinal Fluid Amyloid-Beta, Lactate and Hypocretin in Patients With Hydrocephalus: A Pilot Study.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e70292},
doi = {10.1111/jsr.70292},
pmid = {41607364},
issn = {1365-2869},
support = {//IMK Almene Fund/ ; //Alzheimer's Research Fund Denmark/ ; NNF17OC0024718//Novo Nordisk Fonden/ ; NNF20SA0067242//Novo Nordisk Fonden/ ; R211-2015-2937//Lundbeck Foundation/ ; },
abstract = {This pilot observational study evaluated whether frequent overnight sampling of ventricular cerebrospinal fluid could clarify how sleep, hypocretin and lactate relate to amyloid-β42 dynamics in adults with hydrocephalus. Seven participants underwent hourly ventricular cerebrospinal fluid sampling from early evening to late morning during inpatient monitoring, combined with full polysomnography. Concentrations of amyloid-β42, hypocretin, lactate, melatonin and electrolytes were measured and normalised to each individual's mean. Relationships with sleep stage and circadian patterns were examined using correlation analysis and cosinor modelling. Sleep was markedly disrupted, with obstructive sleep apnea common and analysable sleep data available for six participants. Non-rapid eye movement sleep peaked at approximately 4 AM Amyloid-β42 rose in the evening, plateaued during peak non-rapid eye movement sleep and increased sharply after 8 AM Hypocretin and lactate were positively correlated and each preceded and correlated with amyloid-β42 surges. Melatonin peaked near 6 AM and was associated with non-rapid eye movement sleep. Intracranial pressure displayed a strong circadian rhythm, peaking during non-rapid eye movement sleep, whereas hypocretin and amyloid-β42 exhibited only modest rhythmicity. These findings demonstrate that overnight ventricular cerebrospinal fluid sampling is feasible in adults with hydrocephalus. Preliminary evidence suggests that processes linked to wakefulness, rather than sleep or intrinsic circadian timing, may be the primary drivers of overnight amyloid-β42 variation. Hypocretin pathways may represent potential therapeutic targets in Alzheimer's disease, but conclusions are limited by abnormal sleep architecture and underlying neurological disease. Validation in larger and more representative populations is warranted.},
}

@article {pmid41607305,
year = {2026},
author = {Khatibi, N and MacDonald, JL},
title = {Disrupted Vitamin D Signaling and Metabolism in Neurodevelopmental and Neurodegenerative Disorders.},
journal = {ASN neuro},
volume = {18},
number = {1},
pages = {2617453},
doi = {10.1080/17590914.2026.2617453},
pmid = {41607305},
issn = {1759-0914},
mesh = {Humans ; *Vitamin D/metabolism ; *Neurodegenerative Diseases/metabolism ; *Vitamin D Deficiency/metabolism/complications ; *Signal Transduction/physiology ; Animals ; *Neurodevelopmental Disorders/metabolism ; },
abstract = {Vitamin D is a secosteroid hormone with myriad physiological functions, including pleiotropic effects in the central nervous system. Vitamin D deficiency has been linked to multiple neurodevelopmental and neurodegenerative diseases, including Rett syndrome, epilepsy, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Over the past decades, vitamin D supplementation has been used as a preventative measure or a therapeutic intervention, often with inconsistent or variable responses. We discuss the known association between vitamin D deficiency and neurological disorder occurrence or progression for these disorders. Further, we assess the underlying causes for disruptions in vitamin D levels and the potential mechanisms of vitamin D-mediated improvements. We discuss disruptions in the vitamin D metabolism pathway, signaling, and/or feedback homeostasis that could underpin individual responses to vitamin D supplementation in these disorders. We further discuss the intersection between the vitamin D and cholesterol synthesis pathways and neuroinflammation, and the complex interactions that could contribute to the broad impact of vitamin D on neurological disorders.},
}

Humans
*Vitamin D/metabolism
*Neurodegenerative Diseases/metabolism
*Vitamin D Deficiency/metabolism/complications
*Signal Transduction/physiology
Animals
*Neurodevelopmental Disorders/metabolism

@article {pmid41607243,
year = {2026},
author = {Shih, HH and Lo, CY and Lu, SH and Lin, PC and Lee, KC},
title = {Experiences of bereaved family caregivers of patients with Alzheimer's disease regarding do-not-resuscitate orders: A qualitative study.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e43},
doi = {10.1017/S1478951525100424},
pmid = {41607243},
issn = {1478-9523},
mesh = {Humans ; Female ; Qualitative Research ; Male ; *Caregivers/psychology ; *Alzheimer Disease/psychology/complications ; Taiwan ; Aged ; *Resuscitation Orders/psychology ; Middle Aged ; Aged, 80 and over ; *Bereavement ; Adult ; Decision Making ; Interviews as Topic/methods ; },
abstract = {BACKGROUND: This study aimed to explore the end-of-life decision-making experiences of bereaved family caregivers of Alzheimer's disease (AD) patients, focusing on do-not-resuscitate orders. Given the high emotional and ethical burden on caregivers, understanding their challenges and needs is crucial to enhancing palliative care for AD patients.

METHODS: A qualitative, exploratory study was conducted using semi-structured interviews with 22 family caregivers recruited through purposive sampling in central Taiwan. Participants were primary caregivers for AD patients who had been bedridden for at least a year before death. Analysis employed inductive thematic coding to identify key themes, with rigor ensured through multiple coding, member checking, and reflective journaling.

RESULTS: Three major themes emerged: (1) Decision-making difficulties, where caregivers felt pressure and conflict when making urgent decisions; (2) Willingness to let go, which involved accepting the inevitability of death when recovery was no longer possible; and (3) Embracing the consequences of the decision, reflecting caregivers' sense of relief and acceptance post-decision. Cultural factors, such as filial piety, were found to influence decision-making processes, often intensifying emotional conflicts.

CONCLUSIONS: Findings underscore the importance of early, culturally sensitive discussions around end-of-life care in palliative settings for AD patients. Healthcare providers are encouraged to initiate these discussions, offering clear explanations and emotional support to assist caregivers through decision-making. This study highlights the need for a family-centered approach that respects cultural nuances, helping to reduce caregiver stress and enhance the quality of palliative care in AD contexts.},
}

Humans
Female
Qualitative Research
Male
*Caregivers/psychology
*Alzheimer Disease/psychology/complications
Taiwan
Aged
*Resuscitation Orders/psychology
Middle Aged
Aged, 80 and over
*Bereavement
Adult
Decision Making
Interviews as Topic/methods

@article {pmid41607131,
year = {2026},
author = {Ter Horst, AT and Gerritsen, MJJ and Spikman, JM},
title = {Social Cognition in Community Dwelling Persons With Dementia; Is Facial Emotion Recognition Related to Proxy Rated Empathy and Aggression?.},
journal = {International journal of geriatric psychiatry},
volume = {41},
number = {2},
pages = {e70194},
doi = {10.1002/gps.70194},
pmid = {41607131},
issn = {1099-1166},
mesh = {Humans ; Male ; Female ; Aged ; *Aggression/psychology ; *Dementia/psychology ; *Empathy ; *Facial Recognition/physiology ; *Facial Expression ; Aged, 80 and over ; *Social Cognition ; Independent Living ; Middle Aged ; Neuropsychological Tests ; Executive Function ; Emotions ; Aging in Place ; },
abstract = {OBJECTIVES: Aggressive behaviour and decreased empathy occur in many dementia syndromes. This may be related to lowered overall cognitive functioning which is a common feature of dementia. However, to date, the role of social cognitive impairments such as facial emotion recognition (FER) deficits in dementias other than behavioural variant frontotemporal dementia (bvFTD) remains largely elusive. This study focusses on people who were recently diagnosed with dementia in the memory clinic of a regional hospital, excluding bvFTD. The first question was whether FER was impaired in this group. Next the relation between FER, cognitive functioning and proxy-rated levels of empathic and aggressive behaviour was examined.

METHODS: 80 persons with non-bvFTD dementia were included. FER, overall cognitive functioning, mental speed and executive functioning (mental flexibility, working memory), were measured with respectively The Ekman 60 faces Test, the Mini Mental State Examination (MMSE), the Oral version of the Letter Digit Substitution Test, the Controlled Word Association Test, and the Digit Span test. Empathic and aggressive behaviour were measured using proxy ratings on the Empathic Concern scale of the Interpersonal Reactivity Index, and the Aggression Questionnaire, respectively.

RESULTS: Persons with non-bvFTD dementia were significantly impaired in FER compared to healthy controls, but impaired FER was not significantly related to proxy ratings of aggressive or unempathic behaviour. Neither were cognitive impairments in mental speed and executive functions significantly related to these behaviours. However, we did find a significant association between lower MMSE-scores with higher proxy ratings of unempathic behaviour.

CONCLUSIONS: Levels of emphatic behaviour in persons with non-bvFTD dementia as indicated by proxies might be primarily related to disease severity and not directly to impairments in FER as a measure of social cognition.},
}

Humans
Male
Female
Aged
*Aggression/psychology
*Dementia/psychology
*Empathy
*Facial Recognition/physiology
*Facial Expression
Aged, 80 and over
*Social Cognition
Independent Living
Middle Aged
Neuropsychological Tests
Executive Function
Emotions
Aging in Place

@article {pmid41607060,
year = {2026},
author = {Mastick, ML and Enkhtsetseg, N and Sadok, J and Mochetti, M and Sorby Adams, A and Guo, J and Hacker, CT and Hjerthen, IG and Lee, S and Satish, S and Ham, AS and Hill, J and Balaban, D and Kyle, K and Gillani, RL and Matiello, M and Videnovic, A and Klawiter, EC and Kimberly, WT and Mateen, FJ},
title = {Feasibility and Tolerability of Performing Portable MRI for Neurological Disorders in an Outpatient Neurology Clinic: A Prospective Cohort.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70326},
pmid = {41607060},
issn = {2328-9503},
support = {//Genentech/ ; 2024/03292-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; R01EB031114/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Accessing brain magnetic resonance imaging (MRI) can be challenging, especially for underserved patients, which may lead to disparities in neurological diagnosis.

METHOD: This mixed-methods study enrolled adults with one of four neurological disorders: mild cognitive impairment or dementia of the Alzheimer type, multiple sclerosis (MS), Parkinson disease (PD), or stroke. Participants were enrolled at the Massachusetts General Hospital outpatient clinic in Boston (01/2021-08/2025) and underwent a point-of-care, low-field portable MRI (pMRI) using a 0.064 T scanner (Hyperfine) and pre- and post-scan surveys. For comparison, all participants had received a standard clinical brain MRI of at least 1.5T.

RESULTS: Of the 130 participants (54% male, 46% female), the mean age was 60.6 years (standard deviation (SD) = 17.5). 71% reported at least one barrier to MRI care. The median interval between pMRI and standard MRI brain imaging was 48.5 days (25th, 75th percentiles: 26, 112.5). Participants rated pMRI as highly tolerable, with 93% reporting comfort scores ≥ 7 (on a 10-point scale), and 78% indicating willingness to undergo future pMRI. Mean comfort ratings were significantly higher for pMRI (8.4) compared to traditional MRI (7.5; p < 0.05), though the effect size was moderate (η[2] = 0.096). No differences in tolerability or comfort were observed across disease, age, or sex groups. Common barriers to standard MRI access included transportation, cost, and scheduling, particularly among low-income or unemployed participants. Qualitative feedback emphasized the need for better physical accommodations but broadly supported the acceptability and potential uses of pMRI.

CONCLUSION: These findings support the feasibility, tolerability, and high patient acceptability of pMRI.},
}

@article {pmid41606687,
year = {2026},
author = {Wang, Y and Mohammadi, B and Hartmann, C and Hartmann, K and Thies, E and Matamoros-Angles, A and Fang, C and Harris, DA and Tatzelt, J and Altmeppen, HC and Sepulveda-Falla, D and Strittmatter, SM and Glatzel, M and Krasemann, S},
title = {Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02235-9},
pmid = {41606687},
issn = {2051-5960},
}

@article {pmid41606651,
year = {2026},
author = {Gao, X and Lu, J and Chen, P and Wang, X and Zheng, L and Shao, Y and Shen, H and Yang, Q},
title = {Proximity labeling in neuroscience: decoding molecular landscapes for precision neurology.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {1},
pmid = {41606651},
issn = {2047-9158},
support = {82221001-4//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2023-ZDLSF-52//Key Research and Development Projects of Shaanxi Province/ ; 2022TDGS006//Tangdu Hospital's "Pioneer" Research Initiative Grant/ ; 2025JC-YBQN-1036//Natural Science Basic Research Program of Shaanxi Province/ ; 24YXYJ0124//General Medical Research Program/ ; 2023YFJH006//Phoenix Talent Initiation Program/ ; },
mesh = {Humans ; *Neurosciences/methods ; Animals ; *Neurology/methods ; *Nervous System Diseases/metabolism ; *Precision Medicine/methods ; },
abstract = {The intricate cellular architecture and dynamic molecular interplay in the nervous system have long challenged mechanistic studies of neurological diseases. Conventional approaches often miss the transient, low-affinity, or spatially confined interactions that underlie neural homeostasis and pathogenesis. Proximity labeling (PL) technologies overcome this limitation by enabling in situ capture of these elusive molecular events within living systems. Through spatially restricted biotinylation, PL methods, including engineered biotin ligases (e.g., TurboID), peroxidases (e.g., APEX2), and emerging photocatalytic platforms, allow high-resolution mapping of proteomes and interactomes within defined subcellular compartments, cell types, and cell-cell interfaces. In this review, we systematically outline the principles of PL and its transformative applications in constructing molecular atlases of the nervous system. We highlight how these tools are revolutionizing our understanding of brain function by elucidating pathophysiological mechanisms in Alzheimer's disease, Parkinson's disease and other neurological disorders. Furthermore, we discuss how PL accelerates the translation of basic research into clinical practice by facilitating the discovery of mechanistic biomarkers and druggable targets. Finally, we address current challenges and future directions, including integration with multi-omics and single-cell methodologies, and conclude that PL can advance precision neurology by bridging molecular neurobiology with therapeutic innovation.},
}

Humans
*Neurosciences/methods
Animals
*Neurology/methods
*Nervous System Diseases/metabolism
*Precision Medicine/methods

@article {pmid41606232,
year = {2026},
author = {Xie, Z and Tu, W and Ye, XF and Hua, L and Zhang, X and Feng, N},
title = {The association of Alzheimer's disease-related SNPs with mild cognitive impairment susceptibility in the Chinese population.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-37309-0},
pmid = {41606232},
issn = {2045-2322},
support = {81602929//the National Natural Science Foundation of China/ ; },
abstract = {Previous Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD), whereas their associations with mild cognitive impairment (MCI) remain unclear. To evaluate the associations between 100 representative AD-associated SNPs and susceptibility to MCI in the Chinese population. We recruited 200 MCI patients and 200 cognitively-healthy controls from the community, matched for age and sex. Associations between SNPs and MCI risk were estimated using lasso regression, adjusted for APOE status, using different genetic models. Fifteen SNPs in nine genes (including CLU, SORL1, PICALM, BDNF, NOS3, MTHFR, TOMM40, BIN1, and PVRL2) were associated with MCI in single-SNP analysis. In the multi-SNP association test, rs1801133 and rs9331888 of CLU were consistently associated with MCI risk in the dominant model. TOMM40 rs2075650 (G) was associated with MCI risk in the dominant model by age and education (OR = 2.41, 95%CI = 1.27-4.59), but disappeared when further adjusted for APOEε4 status. PICALM rs561655 (G) (OR = 0.52, 95%CI = 0.30-0.92) and NOS3 rs1549758 (T) (OR = 0.53, 95%CI = 0.30-0.94) were identified as protective genetic factors of MCI for the first time in dominant model combined with the APOEε4 allele. Moreover, MTHFR rs1801133 (A) and CLU rs9331888 (G) showed more susceptibility to MCI in the additive model. SORL1 rs641120(G) showed a protective effect, whereas BIN1 rs5733839 consistently showed a risk effect for MCI in the overdominant model, regardless of APOEε4 status. This study suggests that some AD-associated SNPs are associated with cognitive decline and may have important implications for future studies.},
}

@article {pmid41606102,
year = {2026},
author = {Searson, PC and Banks, WA},
title = {Strategies for blood-brain barrier rejuvenation and repair.},
journal = {Nature reviews. Drug discovery},
volume = {},
number = {},
pages = {},
pmid = {41606102},
issn = {1474-1784},
abstract = {Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical for central nervous system homeostasis and so there are many mechanisms of dysfunction, and hence many targets for intervention. Furthermore, many mechanisms are shared among diseases and disease subtypes, resulting in the potential for common strategies for BBB repair. In this Review, we consider the BBB as a therapeutic target and discuss approaches to its repair and protection in specific disease states and during normal ageing.},
}

@article {pmid41605956,
year = {2026},
author = {Latifi, N and Ahmadi, S and Lotfi, S and Kolahi, SA},
title = {SMILES-based QSAR analysis of carbamate derivatives targeting butyrylcholinesterase.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {3910},
pmid = {41605956},
issn = {2045-2322},
mesh = {*Butyrylcholinesterase/chemistry/metabolism ; *Quantitative Structure-Activity Relationship ; *Carbamates/chemistry/pharmacology ; *Cholinesterase Inhibitors/chemistry/pharmacology ; Humans ; Models, Molecular ; Alzheimer Disease/drug therapy ; },
abstract = {Butyrylcholinesterase (BuChE) is a key enzyme implicated in the pathogenesis of Alzheimer's disease (AD), and its inhibition represents a promising therapeutic strategy for disease management. Among various inhibitor classes, carbamate derivatives have attracted significant attention due to their pseudo-irreversible inhibition mechanism and favorable pharmacological profiles, making them valuable scaffolds in anti-Alzheimer drug discovery. In this study, a dataset of 205 carbamate derivatives was carefully compiled from reliable peer-reviewed literature, and QSAR modeling was performed for the first time on this dataset. Quantitative structure-activity relationship (QSAR) models were constructed to predict the BuChE inhibitory activity (pIC50) employing Monte Carlo optimization within the CORAL-2023 software framework. Hybrid optimal descriptors derived from SMILES notation and hydrogen-suppressed molecular graphs were utilized. Sixty models were developed across four random splits using four distinct target functions (TF0-TF3), among which the TF3-based models exhibited superior statistical performance (validation R[2] ranging from 0.80 to 0.86, Q[2] between 0.78 and 0.84, and RMSE values from 0.45 to 0.54). The mechanistic interpretation of the model showed that the increasing SMILES-based descriptors correspond to key pharmacophoric regions of the BuChE active site, including the PAS, acyl pocket, and catalytic triad. These correlations confirm that aromatic, hydrophobic, and branched fragments enhance inhibitory activity through π-π interactions, hydrophobic anchoring, and optimal orientation toward Ser198.},
}

*Butyrylcholinesterase/chemistry/metabolism
*Quantitative Structure-Activity Relationship
*Carbamates/chemistry/pharmacology
*Cholinesterase Inhibitors/chemistry/pharmacology
Humans
Models, Molecular
Alzheimer Disease/drug therapy

@article {pmid41605321,
year = {2026},
author = {Zhang, H and Xu, Q and Ye, M and Wu, X and Ren, Z and Qin, L and Tang, Z and Wang, G and Xiang, Q and Liu, L},
title = {Inclisiran Attenuates Alzheimer's Disease-like Changes by Suppressing Microvascular Endothelial Ferroptosis to Preserve Blood-Brain Barrier Integrity.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.01.045},
pmid = {41605321},
issn = {1873-4596},
abstract = {The integrity of blood-brain barrier (BBB) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) by regulating Aβ clearance and neurotoxic compound exclusion. Hyperlipidemia exacerbates AD by impairing the BBB function. Inclisiran, a PCSK9-targeting siRNA, reduces cholesterol levels; however, its neuroprotective effects remain unclear. Here, we report the novel discovery that Inclisiran attenuates AD-like changes through the PCSK9-ferroptosis axis in brain microvascular endothelial cells (BMECs). First, integrated bioinformatics analysis and experimental validation of cortical tissues from patients with AD and healthy controls revealed a coordinated upregulation of PCSK9 and β-amyloid (Aβ), accompanied by increased iron deposition and significant activation of the ferroptosis pathway. Interestingly, these changes are located in the BMECs of the blood-brain barrier rather than in the brain parenchyma. Second, in hyperlipidemic ApoE-/- mouse models, integrated application of cerebral microvessel isolation, molecular biology techniques, immunofluorescence co-localization analysis, and behavioral tests demonstrated that Inclisiran significantly reduced AD-like changes by attenuating BBB dysfunction based on the suppression of PCSK9-mediated ferroptosis in BMECs. Third, in vitro studies employing the HCMEC/D3 BBB model with integrated assessments of lipid peroxidation, mitochondrial function, and transwell-based barrier integrity demonstrated that Inclisiran significantly reduced ferroptosis and restored BBB integrity via PCSK9 suppression. Our findings not only establish a novel PCSK9-ferroptosis-BBB regulatory axis in AD pathogenesis but also posit the clinically approved lipid-lowering drug, Inclisiran, as a promising therapeutic candidate for AD, providing new targets and mechanisms for the prevention and treatment of AD.},
}

@article {pmid41605308,
year = {2026},
author = {Stephenson, HG and Betthauser, TJ and Jonaitis, E and Hulle, CV and Kollmorgen, G and Quijano-Rubio, C and Ewers, M and Denecke, J and Ulland, TK and Chin, NA and Okonkwo, OC and Carlsson, CM and Asthana, S and Johnson, SC and Blennow, K and Zetterberg, H and Bendlin, BB},
title = {Higher CSF sTREM2 is related to slower hippocampal atrophy and cognitive decline independently of pTau181 levels.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106468},
doi = {10.1016/j.bbi.2026.106468},
pmid = {41605308},
issn = {1090-2139},
abstract = {Heightened TREM2-dependent microglial activation is thought to protect against the negative effects of Alzheimer's disease (AD) neuropathology, but data in preclinical disease and in the context of aging are lacking. This study examined the association of longitudinal hippocampal atrophy and memory composite scores with baseline sTREM2 in the cerebrospinal fluid (CSF) in two large, well-characterized samples of elderly individuals. It was hypothesized that higher sTREM2 would be associated with slower atrophy and cognitive decline and that this effect would be stronger in those with higher AD neuropathology. Linear mixed effects models predicting hippocampal volume and cognitive decline tested interactions between sTREM2 and time (years since baseline) to see whether higher sTREM2 was associated with slower atrophy and cognitive decline, controlling for pTau181 and its interaction with time. A three-way interaction between pTau181, sTREM2, and time was then added to determine whether AD pathology moderated effects of sTREM2. Results showed that higher sTREM2 was associated with slower hippocampal atrophy and cognitive decline independently of pTau181 levels. Further analysis showed that cognitive effects were moderated by AD pathology levels such that beneficial effects of sTREM2 were stronger at higher levels of AD pathology, though this effect was very small, and the interaction between sTREM2 and time remained significant. These findings suggest that higher TREM2-dependent microglial activation, as indexed by sTREM2, may indicate subtle resilience not just to the effects of AD but to age-related neurodegeneration more broadly.},
}

@article {pmid41604898,
year = {2026},
author = {Ni, H and Xiong, Y and Liu, M and Liu, J and Liu, M and Zhang, L and Zhao, Y and Yi, L and Zhou, R and He, Q and Li, Y and Du, Q and Liu, L and Huang, Y and Ning, W and Zhou, H and Dong, Y},
title = {Sinomenine inhibits oxidative stress to attenuate Alzheimer's disease pathology via α7 nicotinic acetylcholine receptor.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {152},
number = {},
pages = {157779},
doi = {10.1016/j.phymed.2026.157779},
pmid = {41604898},
issn = {1618-095X},
abstract = {BACKGROUND: The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid extracted from the traditional Chinese medicine Qingfengteng (Sinomenium acutum). The anti-inflammatory, antioxidant, and immunomodulatory effects of SIN were confirmed to be closely associated with the α7nAChR.

PURPOSE: This study aimed to investigate whether α7nAChR serves as a pharmacological target of SIN against AD, and to evaluate the neuroprotective effects of SIN both in vivo and in vitro, focusing on the α7nAChR/Nrf2/Keap1 signaling pathway.

METHODS: In this study, the effects of SIN in both APP/PS1 transgenic mice and SH-SY5Y cells subjected to Aβ1-42-induced injury were assessed. The selective antagonist α-bungarotoxin ‌(α-BTX), the agonist nicotine (Nic) of α7nAChR, and α7nAChR siRNA were employed. The cognitive function, Aβ deposition, synaptic plasticity markers, the tau protein phosphorylation, mitochondrial membrane potential, oxidative stress and the α7nAChR/Nrf2/Keap1 signaling pathway were analyzed in vivo and/or in vitro.

RESULTS: SIN significantly enhanced learning and memory abilities in APP/PS1 mice, reduced Aβ plaque deposition and synaptic dysfunction, and inhibited hyperphosphorylation of tau protein and oxidative stress in the brain. In Aβ1-42-induced neuronal injury model, SIN alleviated apoptosis, increased BDNF and ACh levels, inhibited mitochondrial damage, stabilized calcium homeostasis, and suppressed oxidative stress. Meanwhile, SIN disrupted Nrf2-Keap1 binding to promote the Nrf2/HO-1 signaling pathway. Nevertheless, SIN effects above were inhibited by α-BTX. The knockdown of α7nAChR in vitro significantly promoted Nrf2/HO-1 pathway and BDNF expression.

CONCLUSION: SIN exerts neuroprotective effect in APP/PS1 transgenic mice and Aβ1-42-induced neuronal injury by inhibiting oxidative stress via α7nAChR/Nrf2/Keap1 pathway. This study provides evidence for α7nAChR as a new target and the clinical application potential of SIN in AD treatment.},
}

@article {pmid41604675,
year = {2026},
author = {Cho, S and Kaur, B and Lam, K and El Gaamouch, F and Kuncewicz, K and Doering, NP and Wolber, G and Gabr, MT},
title = {Structure-Based Virtual Screening Identifies TREM2-Targeted Small Molecules that Enhance Microglial Phagocytosis.},
journal = {ChemMedChem},
volume = {21},
number = {2},
pages = {e202500718},
doi = {10.1002/cmdc.202500718},
pmid = {41604675},
issn = {1860-7187},
support = {DFG 435233773//Deutsche Forschungsgemeinschaft/ ; },
mesh = {*Receptors, Immunologic/metabolism/agonists/antagonists & inhibitors ; *Membrane Glycoproteins/metabolism/agonists/antagonists & inhibitors ; Structure-Activity Relationship ; *Phagocytosis/drug effects ; *Small Molecule Libraries/chemistry/pharmacology/chemical synthesis ; *Microglia/drug effects/metabolism/cytology ; Animals ; Molecular Structure ; Mice ; Humans ; Dose-Response Relationship, Drug ; Molecular Dynamics Simulation ; Drug Evaluation, Preclinical ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor whose activation promotes phagocytosis and neuroprotection in Alzheimer's disease (AD) and related neurodegenerative disorders. While therapeutic efforts have largely focused on antibodies, small-molecule TREM2 modulators remain limited. Here, we applied a structure-based virtual screening workflow targeting a putative allosteric site on TREM2, guided by PyRod-derived pharmacophores from molecular dynamics simulations. Screening of the Enamine Collection (ESC) yielded 20 candidate compounds, three of which demonstrated binding in TRIC assays. The top hit, EN020, exhibited a KD of 14.2 µM (MST) and 35.9 µM (SPR), and significantly enhanced microglial phagocytosis in BV2 cells, outperforming the known TREM2 agonist VG-3927. A preliminary structure-activity relationship (SAR) study, including synthetic and catalog-derived analogs, highlighted a narrow tolerance for scaffold modifications, with only T2V002 retaining partial TREM2 binding affinity. This work identifies EN020 as a novel small-molecule TREM2 modulator with functional activity, providing a framework for rational optimization toward potential AD therapeutics.},
}

*Receptors, Immunologic/metabolism/agonists/antagonists & inhibitors
*Membrane Glycoproteins/metabolism/agonists/antagonists & inhibitors
Structure-Activity Relationship
*Phagocytosis/drug effects
*Small Molecule Libraries/chemistry/pharmacology/chemical synthesis
*Microglia/drug effects/metabolism/cytology
Animals
Molecular Structure
Mice
Humans
Dose-Response Relationship, Drug
Molecular Dynamics Simulation
Drug Evaluation, Preclinical

@article {pmid41604588,
year = {2026},
author = {Kumar, A and Mondal, T and Ramesh, M and Bhoi, J and Samanta, S and Govindaraju, T},
title = {Griess's Reagent-Based Azo Compounds Ameliorate Multifaceted Toxicity and Ferroptosis in Alzheimer's Disease.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00998},
pmid = {41604588},
issn = {1948-7193},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a growing public health concern globally due to the lack of effective treatments. The primary pathological characteristics of AD include the accumulation of amyloid-β (Aβ) as extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau. Additionally, oxidative stress and neuroinflammation are implicated in the disease's pathogenesis. Developing therapeutic approaches to target multiple pathways or disease routes to address the complex pathological processes driven by Aβ remains challenging. In this context, multifunctional small molecules present a promising therapeutic strategy to address the multiple etiologies of AD. In this study, we designed and synthesized a series of multifunctional azo compounds (ACs) based on Griess's reagent. These compounds modulate amyloid aggregation, suppress oxidative stress, mitigate mitochondrial damage, and provide neuroprotection against Aβ-induced toxicity. Among the ACs, AC5 effectively prevents Aβ-induced ROS generation, as indicated by Nrf2 translocation, and exhibits anti-inflammatory activity by targeting inflammatory mediators, suppressing induced nitric oxide synthase (iNOS) expression, and reducing nitric oxide (NO) generation. Furthermore, AC5 effectively combats ferroptosis via modulating lipid peroxidation and restores the master regulator Gpx4 activity. Our findings suggest that AC5 is a promising therapeutic candidate for addressing the multifaceted pathogenesis of AD.},
}

@article {pmid41604552,
year = {2026},
author = {Suryanarayanan, P and Qiu, Y and Sethi, S and Mahajan, D and Li, H and Yang, Y and Eyigoz, E and Guzmán-Sáenz, A and Platt, DE and Rumbell, TH and Ng, K and Dey, S and Burch, M and Kwon, BC and Meyer, P and Cheng, F and Hu, J and Morrone, JA},
title = {Multi-View Biomedical Foundation Models for Molecule-Target and Property Prediction.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e17840},
doi = {10.1002/advs.202517840},
pmid = {41604552},
issn = {2198-3844},
abstract = {Molecular foundation models hold promise to provide accurate predictions for a large and diverse set of downstream tasks in bio-medical research. Quality molecular representations are key and foundation model development has typically focused on a single representation or molecular view, which may have strengths or weaknesses on a given task. We develop Multi-view Molecular Embedding with Late Fusion (MMELON), an approach that integrates pre-trained graph, image and text foundation models and may be readily extended to additional views and models. The multi-view model performs robustly and is validated on over 120 tasks, including molecular solubility, ADME properties, and activity against G Protein-Coupled receptors (GPCRs). The GPCR model array is leveraged to perform a virtual screen in search of ligands binding to Alzheimer's disease related GPCRs. We identify a number of such targets and employ the multi-view model to select strong binders from a compound screen. Predictions are validated through structure-based modeling and identification of key binding motifs.},
}

@article {pmid41604293,
year = {2026},
author = {Hur, M and Kim, M and Min, S and Lee, CH and Kim, DH},
title = {Cognitive and Mental Health Differences Across Latent Profiles of Religiosity and Spirituality in Korean Older Adults With Mild Cognitive Impairment or Alzheimer's Disease.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {41},
number = {},
pages = {15333175251415119},
doi = {10.1177/15333175251415119},
pmid = {41604293},
issn = {1938-2731},
mesh = {Humans ; *Cognitive Dysfunction/psychology ; *Alzheimer Disease/psychology ; Male ; Aged ; Female ; *Spirituality ; Republic of Korea ; *Depression/psychology ; Aged, 80 and over ; *Mental Health ; },
abstract = {Religiosity and spirituality (R/S) encompass organizational activity, private practice, and intrinsic beliefs, which may relate differently to cognitive and mental health outcomes in older adults. This study identified latent R/S profiles among South Korean older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD), and examined differences in cognitive function, psychological well-being, and depressive symptoms. Latent profile analysis using Duke University Religion Index indicators was conducted with 518 patients (MCI: n = 224; AD: n = 294). In MCI, three classes that differed in well-being and verbal fluency were identified; they showed no differences in depressive symptoms or other cognitive domains. In AD, four classes were identified that differed in the Short Blessed Test and Word List Recall; in these, well-being, depression, and other cognitive outcomes did not differ across classes. These findings underscore the relevance of diverse R/S patterns in individualized care for older adults with neurocognitive disorders.},
}

Humans
*Cognitive Dysfunction/psychology
*Alzheimer Disease/psychology
Male
Aged
Female
*Spirituality
Republic of Korea
*Depression/psychology
Aged, 80 and over
*Mental Health

@article {pmid41582778,
year = {2026},
author = {Mumtaz, and Unnithan, D and Hosseini, H and Ali, J and Khan, MA},
title = {Chitosan nanoparticles for brain targeted nose-to-brain drug delivery in neurodegenerative disease: a comprehensive exploration of advances, limitations and future prospects.},
journal = {Expert opinion on drug delivery},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/17425247.2026.2619090},
pmid = {41582778},
issn = {1744-7593},
abstract = {INTRODUCTION: Neurodegenerative diseases (NDDs), such as Alzheimer's and Parkinson's and epilepsy, cause irreversible nerve cell degradation, resulting in cognitive and motor decline. The blood-brain barrier (BBB) complicates treatment, limiting drug access and causing low bioavailability. Chitosan nanoparticles (CH-NPs) offer a promising solution for improving drug delivery to the brain due to their biocompatibility and ability to enhance intranasal delivery, potentially increasing therapeutic efficacy.

AREAS OF COVERAGE: The review discusses advancements in chitosan-based nanoparticle drug delivery systems for NDDs, highlighting literature from 2015 to 2025. It indicates that chitosan can improve drug uptake in the brain by up to ten times and emphasizes its potential for targeted central nervous system (CNS) delivery due to its unique properties. Additionally, intranasal delivery is a non-invasive method to bypass the BBB and enhance therapeutic precision.

EXPERT OPINION: CH-NPs effectively deliver therapeutics to the CNS, leveraging their mucoadhesive properties and biocompatibility to cross the BBB via intranasal delivery. This platform enhances drug uptake and retention in the brain, addressing challenges faced by traditional therapies for NDDs. Optimizing nanoparticle biomaterial properties and delivery methods could improve therapeutic precision and clinical outcomes.},
}

@article {pmid41606143,
year = {2026},
author = {Javaid, H and Jha, A and Cheema, U and Noor, M and Cheema, S and Arfan, M and Aqeel, M and Habib, E and Saddique, MN and Qadri, M and Shamoon, S},
title = {Dose-Dependent efficacy and safety of Brexpiprazole in agitation associated with dementia in Alzheimer's disease: A systematic review and meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {2},
pages = {208},
pmid = {41606143},
issn = {1590-3478},
mesh = {Humans ; *Alzheimer Disease/complications/drug therapy ; *Psychomotor Agitation/drug therapy/etiology ; *Thiophenes/administration & dosage/adverse effects/pharmacology ; *Quinolones/administration & dosage/adverse effects/pharmacology ; Dose-Response Relationship, Drug ; },
abstract = {BACKGROUND: Agitation is one of the most distressing neuropsychiatric symptoms in patients with dementia due to Alzheimer's disease (AD), significantly impacting patients' quality of life and increasing caregiver burden. Brexpiprazole, a serotonin-dopamine modulator, shows promise for managing agitation. This meta-analysis evaluates the efficacy and safety in managing agitation associated AD.

METHOD: A comprehensive literature search was conducted across PubMed, Cochrane, Scopus, Embase and ClinicalTrials.gov from inception until January 2025. We pooled dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD) with 95% confidence intervals (CI), using random-effects models. Heterogeneity was assessed using I² and X² statistics. A p-value of < 0.05 was considered statistically significant. All the calculations were performed using RevMan 5.4.

RESULT: This meta-analysis included 4 studies involving 1440 patients (944 vs. 496) suffering from agitation associated with dementia in AD. Brexpiprazole significantly reduced agitation on CMAI (MD: -3.94 [-6.21 to -1.67], p < 0.001) and NPI-NH (MD: -0.67 [-1.08 to -0.26], p = 0.002) with optimal efficacy at 2-3 mg/day. SAS scores worsened slightly (MD: 0.38 [0.18-0.58], p = 0.0002) while MMSE (p = 0.06) and CGI-S (p = 0.06) remained stable. No significant differences emerged in serious adverse events, mortality, dizziness, or extrapyramidal effects (all p > 0.05).

CONCLUSION: Brexpiprazole effectively reduces agitation in AD without major safety concerns, though mild motor effects were noted. Study limitations include moderate heterogeneity and short trial durations. Future research should explore long-term outcomes and patient stratification.},
}

Humans
*Alzheimer Disease/complications/drug therapy
*Psychomotor Agitation/drug therapy/etiology
*Thiophenes/administration & dosage/adverse effects/pharmacology
*Quinolones/administration & dosage/adverse effects/pharmacology
Dose-Response Relationship, Drug

@article {pmid41606074,
year = {2026},
author = {Ebrahimian, H and Asadzadeh, F and Rahgozar, M and Kavousi, K},
title = {Diagnosis of Alzheimer's disease with high accuracy via Petri net modeling of signaling pathways.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36585-0},
pmid = {41606074},
issn = {2045-2322},
abstract = {Alzheimer's disease is a complex disorder of the nervous system. Diagnosing this disease is a costly process in which numerous laboratory tests and examinations are conducted. Most computational methods for Alzheimer's disease prediction face low accuracy due to challenges such as a limited number of training samples, noisy/overlapping data, and variability in gene expression. This study presents a reliable computational approach for predicting Alzheimer's disease through a new method of analyzing gene expression profiles from either brain tissue or blood samples. The proposed Petri net-based approach demonstrates superior diagnostic accuracy compared to existing methods across multiple gene expression datasets derived from both blood and brain tissue. The proposed method runs a Petri net model of the signaling pathways involved in complex nervous system disorders. In addition, the Petri net model provides step-by-step tracking of gene activation until the final diagnosis state is reached. An accurate understanding of the functions of the key genes of the signaling pathways involved in brain cell death will play a significant role in the early diagnosis of this complex disease and hopefully will lead to the identification of suitable preventive treatments or drug targets.},
}

@article {pmid41605847,
year = {2026},
author = {Sedighi, M and Shahabi, MH and Amanollahi, A and Alam, K and Shemehsavar, S and Shirzadi, Z and Sabatini, S and Khatoonabadi, AR and Prina, M and Hosseini, AA and Burley, CV and Dunne, J and Mahinrad, S and Dajani, I and Martins, RN and Stephan, BCM and Chaari, A and Sohrabi, HR},
title = {Prevalence of dementia in selected Middle East and North Africa (MENA) countries: A systematic review and meta-analysis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71109},
doi = {10.1002/alz.71109},
pmid = {41605847},
issn = {1552-5279},
mesh = {Humans ; *Dementia/epidemiology ; Middle East/epidemiology ; Africa, Northern/epidemiology ; Prevalence ; Female ; Male ; },
abstract = {Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta-analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI). Fifty-two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61-14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia (8.34%), and Egypt (6.86%). Dementia was more common in women than men (13.84% vs. 8.69%). Dementia is prevalent in MENA, with significant variation across countries. The region's aging population highlights the need for ongoing monitoring of dementia trends.},
}

Humans
*Dementia/epidemiology
Middle East/epidemiology
Africa, Northern/epidemiology
Prevalence
Female
Male

@article {pmid41605840,
year = {2026},
author = {Mohs, RC and Beauregard, DW and Hughes, L and Cordell, CB and Levey, AI and Rathore, S and Seyfried, NT and Johnson, ECB and Nicodemus-Johnson, J and Christensen, J and Wolz, R and Dwyer, J},
title = {Biomarkers in patients with clinical signs of mild cognitive impairment or mild Alzheimer's disease but without amyloid deposits on positron emission tomography: Results from Bio-Hermes Study participants.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71085},
doi = {10.1002/alz.71085},
pmid = {41605840},
issn = {1552-5279},
support = {//AbbVie/ ; //Alzheimer's Drug Discovery Foundation/ ; //Aural Analytics/ ; //Biogen/ ; //Cognivue/ ; //C2N/ ; //Gates Ventures/ ; //Linus Health/ ; //Merck & Co./ ; //Quanterix/ ; //Retispec/ ; //Roche/ ; },
mesh = {Humans ; *Cognitive Dysfunction/diagnostic imaging/metabolism ; *Alzheimer Disease/diagnostic imaging/metabolism ; *Biomarkers/metabolism ; Male ; Female ; Aged ; Positron-Emission Tomography ; Amyloid beta-Peptides/metabolism ; *Brain/diagnostic imaging/metabolism ; Aged, 80 and over ; *Plaque, Amyloid/diagnostic imaging ; Neurofilament Proteins ; Proteomics ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) study participants may present with cognitive impairment who do not have brain amyloid deposits (Aβ-). Identifying predictive biomarkers for non-amyloid-related CI may provide better screening tests for trials seeking only CI Aβ+ participants and new therapy targets.

METHODS: Analysis of the Bio-Hermes biomarker database identified subpopulations of clinically normal, CN Aβ- (n = 313), CI Aβ- (n = 296), and CI Aβ+ (n = 258), and CN Aβ+ (n = 84) participants. Comparative analysis of demographics, clinical assessments, biomarkers, cytokines, and proteomics results was conducted.

RESULTS: Subgroup comparison of CI Aβ- versus CN Aβ- found that neurofilament light most clearly differentiated CI Aβ- from CN Aβ- participants. No other biomarker analysis reached a level of differential significance.

DISCUSSION: Analyses showed many novel biomarkers do not differentiate CI Aβ- from CN Aβ-. New biomarkers are needed to best determine the neuropathology of the clinical presentation of AD.

HIGHLIGHTS: NfL differentiated CN Aβ- versus cognitively impaired Aβ-. Proteomics (two platforms) did not differentially assess cognitively impaired Aβ--. Many novel biomarkers did not differentially assess cognitively impaired Aβ-. New biomarkers are needed to determine the neuropathology of AD clinical presentation.},
}

Humans
*Cognitive Dysfunction/diagnostic imaging/metabolism
*Alzheimer Disease/diagnostic imaging/metabolism
*Biomarkers/metabolism
Male
Female
Aged
Positron-Emission Tomography
Amyloid beta-Peptides/metabolism
*Brain/diagnostic imaging/metabolism
Aged, 80 and over
*Plaque, Amyloid/diagnostic imaging
Neurofilament Proteins
Proteomics

@article {pmid41605825,
year = {2026},
author = {Rodriguez, AD and DuBose, JR and Rozga, A and Zimring, CM and Mynatt, ED and Clifford, GD and Vickers, KL and Goldstein, FC and Giannotto, EL and Thelin, J and Levey, AI},
title = {Rationale and design of a multidomain lifestyle program for mild cognitive impairment.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71068},
doi = {10.1002/alz.71068},
pmid = {41605825},
issn = {1552-5279},
support = {//The James M. Cox Foundation/ ; //Cox Enterprises, Inc./ ; },
mesh = {*Cognitive Dysfunction/therapy/psychology ; Humans ; *Life Style ; Quality of Life ; },
abstract = {The development of non-pharmacological treatment approaches is supported by evidence that addressing key modifiable risk factors may prevent or delay up to 45% of dementia cases. The Charlie and Harriet Shaffer Cognitive Empowerment Program (CEP) was developed to address current gaps in access to, and evidence for, interventions that reduce lifestyle risk factors and improve quality of life in individuals with mild cognitive impairment (MCI). Co-designed with patients and families, clinicians, researchers, and industry professionals, the CEP is situated in a conceptual framework that guides assessments and interventions/supports to holistically address the experience of living with MCI. CEP comprises four cores (Therapeutic Programs, Technology, Built Environment, and Innovation Accelerator) that map to the conceptual framework. We contend that our approach provides an opportunity to contribute to the evidence base for multidomain lifestyle programs and gain a deeper understanding of MCI and how individuals can be empowered to manage it. HIGHLIGHTS: The cognitive empowerment program (CEP) is a multidomain lifestyle program that was developed using a co-design process and a conceptual framework that holistically addresses the experience of living with mild cognitive impairment (MCI). CEP provides comprehensive assessment and intervention/support through four cores that map to the conceptual framework: therapeutic programs, technology, built environment and research innovation. CEP's unique approach provides an opportunity to build the evidence base for multidomain lifestyle interventions and to develop and refine lifestyle biomarkers that can be used for early detection of MCI, tracking of disease progression, and objective measurement of the impact of lifestyle interventions.},
}

*Cognitive Dysfunction/therapy/psychology
Humans
*Life Style
Quality of Life

@article {pmid41605754,
year = {2026},
author = {Ferré-González, L and Peña-Bautista, C and Álvarez-Sánchez, L and Peretó, M and García-Vallés, L and Raga, L and Roca, M and Baquero, M and Cháfer-Pericás, C},
title = {Plasma lipidomics in women with Alzheimer's disease: Exploring associations with ApoE genotype and cardiovascular risk.},
journal = {Journal of clinical lipidology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacl.2025.12.025},
pmid = {41605754},
issn = {1933-2874},
abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, with an increasing incidence due to population aging. Approximately two-thirds of the people affected are women, possibly due to biological and hormonal factors. Also, lipids could play an important role in AD and show associations with cognitive impairment. apolipoprotein E allele 4 (ApoE ε4) genotype and cardiovascular (CV) risk lipid ratios could be relevant in lipidomic studies.

OBJECTIVE: This work aims to identify specific alterations in plasma lipid profiles associated with AD in women and to explore these alterations related to Apolipoprotein E (ApoE) and 2 CV risk lipid ratios.

METHODS: A lipidomic mass spectrometry-based method was applied to plasma samples from a clinical cohort of women. The patients were accurately classified into AD (n = 76) and non-AD (n = 74) groups by cerebrospinal fluid amyloid beta (Aβ)42/Aβ40 levels. The identified lipid species were evaluated and grouped into families and subfamilies. The lipids with significant differences between groups were examined in relation to ApoE genotype and 2 CV risk ratios (total cholesterol/high-density lipoprotein [HDL], triglycerides/HDL).

RESULTS: Fatty acyls and monoacylglycerols showed higher levels in AD compared with non-AD, while diacylglycerols (DAGs) showed lower levels in AD. Also, specific subfamilies correlated with aging, CV risk, AD biomarkers, and cognitive status. Of the 627 lipid species detected, 45 showed statistically significant differences between groups, and some of them [lysophosphatidylcholine (24:1), diacylglycerol (18:0/18:1), and triacylglycerol (50:3)] showed significant associations with ApoE genotype and CV risk.

CONCLUSION: This study identified associations between lipid profiles in women and AD pathology, ApoE ε4 genotype, and high CV risk ratios.},
}

@article {pmid41605610,
year = {2026},
author = {Oreskovic, E and Petzold, A and Petropoulos, IN and Hau, S},
title = {Corneal confocal microscopy as a paraclinical test in neurodegenerative disease: a scoping review.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328181},
pmid = {41605610},
issn = {1468-2079},
abstract = {Corneal confocal microscopy (CCM) is a non-invasive imaging technique that enables quantification of the corneal sub-basal nerve plexus and has emerged as a potential surrogate biomarker for peripheral neurodegeneration. This scoping review evaluated current evidence on the use of CCM in assessing corneal nerve fibre changes across neurodegenerative diseases (NDDs) and explored its potential as a paraclinical diagnostic and monitoring tool. A comprehensive search of PubMed and Scopus was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines to identify studies reporting quantitative CCM metrics, including corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL). Both cross-sectional and longitudinal studies of patients with NDDs were included, and findings were narratively synthesised. 50 studies were included: Parkinson's disease (n=13), multiple sclerosis (n=11), cerebrovascular accidents (n=7), post-COVID-19 neuropathy (n=5), amyotrophic lateral sclerosis (n=4), chronic inflammatory demyelinating polyneuropathy (n=4), Alzheimer's disease (n=3), Fabry disease (n=2) and neurofibromatosis type 1 (n=1). CNFL and CNFD were consistently reduced in Parkinson's disease, multiple sclerosis, cerebrovascular accidents, amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy and post-COVID-19 neuropathy, whereas CNBD results were inconsistent. The strongest evidence supported the role of CCM in Parkinson's disease and multiple sclerosis. CNFL and CNFD emerged as the most reliable CCM-derived metrics across NDDs, supporting their potential as objective biomarkers for neurodegeneration. While findings support the potential of CCM as a paraclinical diagnostic tool, methodological heterogeneity in image acquisition, analysis software and study design limited comparability. Standardised imaging and analysis protocols are needed to enable broader clinical application and validation across NDDs.},
}

@article {pmid41605509,
year = {2026},
author = {Li, J and Chen, X and Yang, Y and Xu, Y and Lai, M and Shi, L and Lin, X and Chen, W and Peng, H},
title = {Electron Transfer Mechanism-Mediated Host-Guest Nanoswitch Powered Amplification-Free CRISPR/Cas12a-Electrochemiluminescence Bioassay for Alzheimer's Disease Diagnosis.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c06614},
pmid = {41605509},
issn = {1520-6882},
abstract = {Developing a high-performance amplification-free electrochemiluminescence (ECL) assay platform that operates at a low trigger potential is a promising strategy for broadening the applications of ECL sensing. In this work, we present a host-guest interaction-mediated split-type CRISPR/Cas12a-ECL assay platform by using the highly sensitive host-guest recognition between the β-cyclodextrin-functionalized gold nanoclusters (β-CD-AuNCs) probe and methylene blue (MB) system as a proof of concept. Efficient ECL quenching of β-CD-AuNCs by MB is achieved via an electron transfer mechanism based on host-guest recognition between them. By integrating the high-specific recognition and cleavage activity of the CRISPR/Cas technology, the high quantum yield, and low trigger potential β-CD-AuNCs-based ECL probes, together with the highly sensitive and selective host-guest recognition-based split-type assay design, a novel "trinity" detection platform has been successfully constructed. Using Amyloid-β oligomers (AβOs), a key biomarker for Alzheimer's disease (AD) diagnosis and therapy, as the analyte, this amplification-free CRISPR/Cas-ECL biosensing platform enables ultrasensitive and accurate detection of AβO without requiring additional signal amplification strategies. The proposed sensing platform exhibits a linear detection range from 1.0 × 10[-8] to 1.0 × 10[-1] μg/mL for AβO detection, with a detection limit as low as 0.2 fg/mL (S/N = 3). This sensitivity approaches single-molecule levels and is 3-4 orders of magnitude lower than that of traditional ELISA. Furthermore, owing to its outstanding performance including high specificity, excellent selectivity, superior sensitivity, and strong anti-interference capability, the platform demonstrates remarkable detection performance in monitoring AβO in clinical AD blood samples, showing a good Pearson's correlation between the method and ELISA results. This work provides a powerful tool for clinical diagnosis and paves the way for therapeutic development, while also offering a rational design strategy for next-generation ECL biosensing platforms.},
}

@article {pmid41605352,
year = {2026},
author = {Wang, Y and Mjc, DG and Liang, J and Msn, MJ and Mph, YZ and Bachelor, YP and Zhang, W and Wang, Z and Yang, F and Zheng, F and Xie, W},
title = {Associations of mental and behavioral disorders due to tobacco and alcohol use with incident dementia.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {121239},
doi = {10.1016/j.jad.2026.121239},
pmid = {41605352},
issn = {1573-2517},
abstract = {BACKGROUND: While smoking and drinking are known to influence cognitive function, the future risk of incident dementia among individuals diagnosed with mental and behavioral disorders due to tobacco use (MBT) and mental and behavioral disorders due to alcohol use (MBA) remains unclear.

METHODS: Data were sourced from the UK Biobank, a publicly accessible database in the United Kingdom. The analysis included 362,934 participants free of dementia at baseline. MBT and MBA were identified using ICD-10 codes from first occurrence data in the UK Biobank dataset. Dementia outcomes, defined algorithmically by the UK Biobank, included all-cause dementia, Alzheimer's disease, and vascular dementia. Cox regression models assessed the associations of MBT and MBA with incident dementia.

RESULTS: Among only smoking participants, those with MBT had an adjusted hazard ratio (HR) of 1.47 (95% confidence interval [CI]: 1.10-1.96) for all-cause dementia, compared with non-MBT participants. Among only drinking participants, those with MBA had an adjusted HR of 2.34 (95% CI: 2.05-2.68) for all-cause dementia, compared with non-MBA participants. Among both smoking and drinking participants, those with both MBT and MBA (HR = 3.86, 95% CI: 2.78-5.35), those with only MBT (HR = 1.31, 95% CI: 1.02-1.67), and those with only MBA (HR = 2.46, 1.39-4.35) had a significantly higher risk of incident dementia, compared with non-MBT and non-MBA participants.

CONCLUSIONS: Individuals diagnosed with MBT, MBA, or both are associated with a higher likelihood of incident dementia. These findings underscore the need for interventions targeting these behaviors to mitigate the dementia incidence.},
}

@article {pmid41605332,
year = {2026},
author = {Neupane, SP and Onyeka, IN and Bull, VH and Daray, FM},
title = {Associations between diseases of the mouth and mental disorders: A scoping review of longitudinal studies.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107285},
doi = {10.1016/j.nbd.2026.107285},
pmid = {41605332},
issn = {1095-953X},
abstract = {BACKGROUND: Mental disorders and oral health conditions frequently co-occur. We mapped and critically reviewed the literature on longitudinal associations between oral health conditions and mental disorders.

METHOD: MEDLINE, Embase and PsycInfo were searched for longitudinal studies published during the last 25 years. Two reviewers independently screened, reviewed full-text and extracted data before synthesizing the evidence. Associations between oral and mental disorders were illustrated as Sankey diagrams. The review protocol was pre-registered (https://osf.io/vrpu9).

FINDINGS: From 165 included studies, we identified 118 studies investigating 35 independent associations between 16 oral exposures and 12 mental disorder outcomes. Another 42 studies investigated 32 associations between 17 mental disorder exposures and 14 oral outcomes. Five studies reported bidirectional associations. Most reports linked tooth loss to Alzheimer's disease/other dementias (18 studies) and cognitive impairment (15 studies), with periodontitis linked to Alzheimer's disease/other dementias (16 studies). Conversely, depression (10 studies), dementia (6 studies) and sleep disorder (5 studies) were attributed to temporomandibular disorders (TMD; 10 studies), periodontitis (8 studies) and caries (7 studies) outcomes. Depressive and anxiety disorders were linked bidirectionally with TMD and eating disorders.

INTERPRETATION: Prevention and early management of oral and mental disorders may mitigate their reciprocal risk, thereby lowering the overall disease burden.},
}

@article {pmid41604985,
year = {2026},
author = {Akbari, A and Nasrolahzadeh, M and Haddadnia, J},
title = {Early diagnosis of Alzheimer's disease from functional rs-fMRI images based on deep learning networks and transfer learning approach.},
journal = {Psychiatry research. Neuroimaging},
volume = {357},
number = {},
pages = {112151},
doi = {10.1016/j.pscychresns.2026.112151},
pmid = {41604985},
issn = {1872-7506},
abstract = {Exploiting deep learning methods to accelerate the analysis of medical images and the interpretation of pathology results for early diagnosis of Alzheimer's disease (AD) has recently attracted great attention. However, challenges like sub-optimal classifiers and poor image representation hinder their effectiveness. Computer-aided diagnosis (CADx) can improve performance by classifying patterns. Despite the drawbacks of deep networks such as Visual Geometric Group (VGG), including long processing times and performance issues due to data distribution, many CADx systems still rely on VGG classifiers due to their potential for high accuracy when properly trained. To tackle these issues, this paper introduces two novel deep networks, called optimized VGG-16 (OVGG-16) and optimized VGG-19 (OVGG-19), in light of the concepts of transfer learning and dense layers to improve diagnosis performance. The proposed system was developed for the diagnosis of AD employing the OVGG-16 and OVGG-19 networks as classifiers from rs-fMRI images. The results show that the convergence rate of the proposed OVGG-16 and OVGG-19 networks is more rapid than that of the conventional VGG-16 and VGG-19. Moreover, the proposed system, which uses the OVGG-16 network, yielded a high accuracy of 100% and 98.83% for binary and multiclass classification, respectively, which surpasses existing state-of-the-art approaches.},
}

@article {pmid41604947,
year = {2026},
author = {Ranjan, S and Badal, R and Yadav, P and Kumar, L},
title = {Dementia severity index: A threshold-based approach to classifying dementia levels using resting state EEG.},
journal = {Computers in biology and medicine},
volume = {203},
number = {},
pages = {111505},
doi = {10.1016/j.compbiomed.2026.111505},
pmid = {41604947},
issn = {1879-0534},
abstract = {BACKGROUND: Alzheimer's Disease (AD) and FrontoTemporal Dementia (FTD) are dementia conditions that often overlap clinically, leading to misdiagnoses. Traditional questionnaires are subjective and time-intensive, while neuroimaging is costly and less accessible. EEG-based methods offer a cost-effective alternative but primarily focus on spectral and source analyses, with a limited exploration into quantitative range identification for differentiating dementia states.

METHODS: This study presents a threshold-based approach to dementia-level classification using resting-state EEG. In particular, an algorithm is presented for threshold computation followed by Dementia Severity Index (DSI) formulation. Two potential biomarkers for cognitive decline that capture band-specific alterations are explored. These biomarkers form the basis of the DSI, categorizing individuals into AD, FTD, or Healthy Control (HC). The classification performance of the proposed DSI is evaluated comprehensively using multiple machine learning classifiers and subject validation strategies.

RESULTS: The proposed DSI-based approach achieves classification accuracies of 81.62% using kNN. The approach reliability is validated across three diverse EEG datasets and through threshold variation analysis. Furthermore, the relationship between EEG features and cognitive performance is analyzed using Spearman's correlation. A significant correlation of 0.79 and 0.62 is obtained between predicted and actual MMSE.

CONCLUSION: The proposed DSI effectively differentiates AD, FTD, and HC, providing a robust threshold-based framework for dementia assessment. It enhances interpretability by assigning quantitative values to dementia states and reduces subjective reliance. This study offers a potential EEG-based biomarker suitable for clinical settings, offering minimal stress to patients during assessments.},
}

@article {pmid41604700,
year = {2026},
author = {Qi, Z and Li, Q and Cao, J and Xu, B and Jiang, F and Wang, Y and Wu, D and Li, G},
title = {Chronic Exposure to Thermally Processed Food-Derived Carbon Polymers Accelerated Neuroinflammation in Alzheimer Disease Mice through Microbe-Gut-Brain Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c11423},
pmid = {41604700},
issn = {1520-5118},
abstract = {Processed foods are increasingly associated with the prevalence of neurodegenerative diseases, including Alzheimer disease (AD). Therefore, it is essential to elucidate the underlying mechanisms by which these processed foods influence AD. This study identified and isolated an emerging dietary risk factor, carbon-based polymers (CPs), from processed foods, specifically roasted lamb. Further investigation revealed that prolonged exposure to CPs induced gut microbiota dysbiosis along with elevated endotoxin production and perturbed tryptophan metabolism, thereby leading to intestinal inflammation. These alterations facilitated the entry of LPS into the blood circulation, which subsequently triggered systemic inflammation and increased the blood-brain barrier permeability. Ultimately, they accelerated neuroinflammation and synaptic dysfunction in transgenic APPswe/PSEN 1dE9 mice via the LPS-TLR4-NF-κB signaling pathway. Collectively, this study advances our understanding of CPs as potential accelerators of neuroinflammation, providing a scientific basis for reevaluating the biosafety of dietary CPs in humans, especially for at-risk populations.},
}

@article {pmid41604668,
year = {2026},
author = {Fantus, S and Li, J and Wang, T and Tang, L},
title = {Ethical Knowledge, Challenges, and Institutional Strategies Among Medical AI Developers and Researchers: Focus Group Study.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e79613},
doi = {10.2196/79613},
pmid = {41604668},
issn = {1438-8871},
mesh = {*Artificial Intelligence/ethics ; Focus Groups ; Humans ; *Research Personnel ; Male ; Female ; },
abstract = {BACKGROUND: As artificial intelligence (AI) becomes increasingly embedded in clinical decision-making and preventive care, it is urgent to address ethical concerns such as bias, privacy, and transparency to protect clinician and patient populations. Although prior research has examined the perspectives of medical AI stakeholders, including clinicians, patients, and health system leaders, far less is known about how medical AI developers and researchers understand and engage with ethical challenges as they develop AI tools. This gap is consequential because developers' ethical awareness, decision-making, and institutional environments influence how AI tools are conceptualized and deployed in practice. Thus, it is essential to understand how developers perceive these issues and what supports they identify as necessary for ethical AI development.

OBJECTIVE: The objectives of the study were twofold: (1) to examine medical AI developers' and researchers' knowledge, attitudes, and experiences with AI ethics; and (2) to identify recommendations to enhance and strengthen interpersonal and institutional ethics-focused training and support.

METHODS: We conducted 2 semistructured focus groups (60-90 minutes each) in 2024 with 13 AI developers and researchers affiliated with 5 US-based academic institutions. Participants' work spanned a wide variety of medical AI applications, including Alzheimer disease prediction, clinical imaging, electronic health records analysis, digital health, counseling and behavioral health, and genotype-phenotype modeling. Focus groups were conducted via Microsoft Teams, recorded, and transcribed verbatim. We applied conventional qualitative content analysis to inductively identify emerging concepts, categories, and themes. Coding was performed independently by 3 researchers, with consensus reached through iterative team meetings.

RESULTS: The analysis identified four key themes: (1) AI ethics knowledge acquisition: participants reported learning about ethics informally through peer-reviewed literature, reviewer feedback, social media, and mentorship rather than through structured training; (2) ethical encounters: participants described recurring ethical challenges related to data bias, patient privacy, generative AI use, commercialization pressures, and a tendency for research environments to prioritize model accuracy over ethical reflection; (3) reflections on ethical implications: participants expressed concern about downstream effects on patient care and clinician autonomy, and model generalizability, noting that rapid technological innovation outpaces regulatory and evaluative processes; and (4) strategies to mitigate ethical concerns: recommendations included clearer institutional guidelines, ethics checklists, interdisciplinary collaboration, multi-institutional data sharing, enhanced institutional review board support, and the inclusion of bioethicists as members of the AI research team.

CONCLUSIONS: Medical AI developers and researchers recognize significant ethical challenges in their work but lack structured training, resources, and institutional mechanisms to address them. Findings of this study underscore the need for institutions to consider embedding ethics into research processes through practical tools, mentorship, and interdisciplinary partnerships. Strengthening these supports is essential to preparing the next generation of developers to design and deploy ethical AI in health care.},
}

*Artificial Intelligence/ethics
Focus Groups
Humans
*Research Personnel
Male
Female

@article {pmid41604611,
year = {2026},
author = {Rani, N and Moghekar, A and Callow, DD and Alm, KH and Pettigrew, C and Soldan, A and Miller, M and Wang, J and Lodge, MA and Albert, M and Bakker, A},
title = {Association Between Longitudinal Rate of Change in CSF Biomarkers and Subsequent Tau PET Burden in Early Braak Stages.},
journal = {Neurology},
volume = {106},
number = {4},
pages = {e214620},
doi = {10.1212/WNL.0000000000214620},
pmid = {41604611},
issn = {1526-632X},
mesh = {Humans ; *tau Proteins/cerebrospinal fluid/metabolism ; Female ; Male ; Positron-Emission Tomography ; Biomarkers/cerebrospinal fluid ; Aged ; Longitudinal Studies ; Amyloid beta-Peptides/cerebrospinal fluid ; *Alzheimer Disease/cerebrospinal fluid/diagnostic imaging/pathology ; Retrospective Studies ; Middle Aged ; Disease Progression ; Peptide Fragments/cerebrospinal fluid ; },
abstract = {BACKGROUND AND OBJECTIVES: Changes in CSF and tau PET biomarkers of Alzheimer disease (AD) emerge years before clinical symptoms are observed. However, few studies have examined the temporal relationship between these measures. This study investigated whether longitudinal changes in CSF AD biomarkers were associated with [18]F-MK6240 tau PET measures in early Braak stage subregions.

METHODS: This study involved a retrospective analysis of cognitively unimpaired participants from the longitudinal observational Biomarkers of Cognitive Decline Among Normal Individuals cohort (NIH and Johns Hopkins University). Phosphorylated tau (p-tau) 181, total tau (t-tau), and β-amyloid (Aβ)42/Aβ40) measures were obtained from CSF collected biennially over a mean of 12.8 years before tau PET acquisition. Linear mixed-effect models examined how previous CSF biomarker levels and rates of change in these measures related to subsequent tau deposition corresponding to Braak stages I and II.

RESULTS: A total of 120 cognitively unimpaired individuals (baseline age range 32-78 years; mean age 57 years; 60% female) were included in the analysis, including 78 participants with longitudinal CSF data (424 observations) and 42 additional participants contributing to cross-sectional analyses of initial CSF levels only. Results showed that higher levels of CSF p-tau181 (β = 0.567 [0.411-0.724]; β = 0.508 [0.344-0.671]) and t-tau (β = 0.411 [0.260-0.562]; β = 0.393 [0.240-0.547]), as well as steeper previous rates of increase in p-tau181 (β = 0.016 [0.008-0.024]; β = 0.018 [0.011-0.025]) and t-tau (β = 0.015 [0.009-0.022]; β = 0.016 [0.010-0.022]), were significantly associated with subsequent higher tau PET burden in Braak stages I and II. By contrast, although lower Aβ42/Aβ40 levels were associated with subsequent tau burden (β = -0.556 [-0.706 to -0.406]; β = -0.503 [-0.653 to -0.353]), the rate of change in Aβ42/Aβ40 over time was not.

DISCUSSION: These findings show that tau PET burden in Braak stage I and II subregions is associated with increases in CSF tau and p-tau over time, offering important insights into the relationships among key biomarkers for the diagnosis and staging of AD, although tau PET was collected at only a single time point, limiting inferences about the temporal evolution of PET-CSF relationships.},
}

Humans
*tau Proteins/cerebrospinal fluid/metabolism
Female
Male
Positron-Emission Tomography
Biomarkers/cerebrospinal fluid
Aged
Longitudinal Studies
Amyloid beta-Peptides/cerebrospinal fluid
*Alzheimer Disease/cerebrospinal fluid/diagnostic imaging/pathology
Retrospective Studies
Middle Aged
Disease Progression
Peptide Fragments/cerebrospinal fluid

@article {pmid41604486,
year = {2026},
author = {Maaser-Hecker, AK and Zellmer, JC and Kim, M and Bakiasi, G and Maiti, AK and Curtat, MPC and Choi, SH and Prokopenko, D and Tanzi, RE and Bhattacharyya, R},
title = {RIN3 mutations impairing binding of the Alzheimer's disease-associated protein BIN1 lead to RAB5 hyperactivation and endosomal pathology.},
journal = {Science advances},
volume = {12},
number = {5},
pages = {eadx2127},
doi = {10.1126/sciadv.adx2127},
pmid = {41604486},
issn = {2375-2548},
mesh = {*rab5 GTP-Binding Proteins/metabolism/genetics ; *Alzheimer Disease/metabolism/genetics/pathology ; *Endosomes/metabolism/pathology ; Animals ; Humans ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mice ; *Tumor Suppressor Proteins/metabolism/genetics ; *Mutation ; Protein Binding ; *Nuclear Proteins/metabolism/genetics ; Neurons/metabolism ; Mice, Knockout ; Induced Pluripotent Stem Cells/metabolism ; Nerve Tissue Proteins ; },
abstract = {Alzheimer's disease (AD) risk is strongly influenced by genetic variants that converge on pathways regulating endosomal homeostasis. Among these, BIN1 and RIN3 have emerged as susceptibility genes, yet their functional relationship in AD remains largely unknown. Here, we investigated how BIN1 and RIN3 interaction regulates RAB5 activity and endosomal pathology. RIN3 has been shown to bind BIN1, and we previously reported that this interaction modulates amyloid-β (Aβ) precursor protein (APP) trafficking and Aβ generation in vitro. To extend these findings, we used Rin3 constitutive knockout (Rin3-CKO) mice and CRISPR-Cas9-edited human induced pluripotent stem cell-derived neurons carrying either BIN1 knockout or rare familial AD RIN3 missense mutations within the BIN1-binding domain. We found that disruption of BIN1-RIN3 binding, through either genetic deletion or pathogenic RIN3 variants, resulted in RIN3-mediated RAB5 hyperactivation and enlargement of neuronal endosomes, a hallmark of early AD pathology. Transcriptomic profiling further revealed dysregulated expression of AD-related genes. Together, these findings establish BIN1 as a critical regulator of RIN3-driven RAB5 activation and neuronal endosomal homeostasis.},
}

*rab5 GTP-Binding Proteins/metabolism/genetics
*Alzheimer Disease/metabolism/genetics/pathology
*Endosomes/metabolism/pathology
Animals
Humans
*Adaptor Proteins, Signal Transducing/metabolism/genetics
Mice
*Tumor Suppressor Proteins/metabolism/genetics
*Mutation
Protein Binding
*Nuclear Proteins/metabolism/genetics
Neurons/metabolism
Mice, Knockout
Induced Pluripotent Stem Cells/metabolism
Nerve Tissue Proteins

@article {pmid41604360,
year = {2026},
author = {Chen, YH and Li, S and Yu, C and Liao, Y and Wang, LN and Yang, B},
title = {A Global, Regional, and National Survey on Burden and Quality of Care Index of Alzheimer's Disease and Other Dementias in Adults Aged 55 and Above: The Global Burden of Disease Study 1990-2021.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-15},
doi = {10.1159/000549913},
pmid = {41604360},
issn = {1423-0208},
abstract = {BACKGROUND: Alzheimer's disease and other dementias (ADOD) represent a growing global health challenge. This study aims to propose a comprehensive measure called the quality of care index (QCI) to assess disparities in quality of care (QC) for ADOD patients across global, regional, and national levels. We also evaluate temporal trends in QCI and explore associations with socioeconomic development, gender, and age.

METHODS: Individuals aged 55 years and older with ADOD were included in this longitudinal study using data from the global burden of disease (GBD) database spanning 1990-2021. The QCI score was calculated using four indicators. Principal component analysis was employed to compute the QCI. The QCI was rescaled to a single index ranging from 0 to 100, where higher scores indicate better QC.

RESULTS: The global QCI increased from 32.9 in 1990 to 50.2 in 2021, with a greater increase among females (68.8%) than males (52.4%). Significant gains were observed in regions with middle and high-middle sociodemographic index), while slight declines occurred in high- and low-middle SDI regions, and slow progress was seen in low SDI regions. The gender gap in QCI narrowed, with females outperforming males in low SDI regions. QCI scores showed a marked increase with age, reflecting lower QC access in younger age groups and a sharp rise in older age groups.

CONCLUSION: Substantial disparities in QCI exist globally and regionally across age cohorts and between men and women. Policymakers should prioritize targeted interventions to address these gaps, improve access to high-quality care, and alleviate the global burden of ADOD.},
}

@article {pmid41604235,
year = {2026},
author = {Al-Ameer, HJ and Basheer, NM and H, M and Shankhyan, A and Panigrahi, R and Arora, V and Azizjanov, K and Eshchanov, E and Ataullaev, Z},
title = {Neuroimmune Cross-Talk and Multilevel Cascades in Fentanyl Toxicity: Interplay of Hypoxic Stress, Glial Activation, and Synaptic Dysregulation in Systems-Level Neurodegeneration.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70069},
pmid = {41604235},
issn = {1099-1263},
abstract = {Fentanyl, an ultra-potent synthetic opioid, has traditionally been characterized by its acute toxic effects, particularly respiratory depression. However, accumulating research indicates that its neurobiological influence extends far beyond its short pharmacological window, intersecting with several core mechanisms implicated in major neurodegenerative disorders. This review integrates multiscale evidence to propose a unified conceptual framework in which fentanyl may function not only as an acute neurotoxin but also as a putative accelerator of long-term neurodegenerative vulnerability. Drawing from molecular signaling, cellular stress pathways, glial-neuronal cross-talk, neurovascular regulation, synaptic architecture, and large-scale neural networks, we highlight fentanyl's capacity to trigger a convergent cascade encompassing hypoxic-metabolic reprogramming, mitochondrial fragmentation, TLR4-NF-κB-driven inflammation, NLRP3 inflammasome activation, complement-mediated synaptic pruning, astrocytic EAAT2 downregulation, and blood-brain barrier compromise. These alterations propagate through recursive cross-talk loops that progressively diminish neuronal resilience, destabilize oscillatory coherence, and weaken circuit-level adaptability. Importantly, mechanistic overlaps with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis suggest that fentanyl exposure may be mechanistically associated with processes capable of accelerating disease onset, exacerbating progression, or unmasking latent vulnerabilities, particularly in genetically or metabolically predisposed individuals. By reframing fentanyl as a systems-level destabilizer capable of imprinting persistent neurobiological changes, this model underscores the need for comprehensive biomarker development, longitudinal risk assessment, and targeted neuroprotective interventions. The integrative framework presented herein offers a foundation for predicting the long-term neurological consequences of fentanyl exposure and calls for urgent reconsideration of its role in population-level neurodegenerative risk.},
}

@article {pmid41603996,
year = {2026},
author = {Naderian, R and Nazari, MA and Meybodi, TE and Paraandavaji, E and Lagzian, A and Nikandish, M and Eslami, M},
title = {Redox signaling in the heart and brain: the roles of nitric oxide and reactive oxygen species in disease and therapy.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {23},
pmid = {41603996},
issn = {1573-7365},
mesh = {Humans ; *Reactive Oxygen Species/metabolism ; *Nitric Oxide/metabolism ; *Signal Transduction/physiology ; Oxidation-Reduction ; *Brain/metabolism ; Animals ; Oxidative Stress/physiology ; *Myocardium/metabolism ; Antioxidants/therapeutic use ; Cardiovascular Diseases/metabolism ; },
abstract = {Nitric oxide (NO) and reactive oxygen species (ROS) are central to the pathophysiology of cardiovascular and neurological disorders, influencing intricate signaling pathways that manage vascular function, inflammation, and oxidative stress. NO, predominantly produced by NO-synthases, plays a vital role in maintaining vascular health by facilitating vasodilation and preventing platelet aggregation. However, its reaction with superoxide results in the formation of peroxynitrite, a highly reactive molecule that intensifies oxidative damage and impairs endothelial function. Elevated ROS levels, arising from sources like NADPH oxidases and mitochondrial activity, further heighten oxidative stress, driving the progression of conditions like atherosclerosis and neurodegenerative diseases. Therapeutic strategies aimed at restoring the balance between NO and ROS include the use of antioxidants to neutralize ROS, pharmacological methods to enhance NO bioavailability, and nanoparticle-based systems designed to address oxidative stress. Emerging research points to potential of targeting redox-sensitive pathways, such as the Keap1-Nrf2 axis, to slow disease progression. In neurological disorders, overproduction of ROS leads to neuroinflammation and neuronal apoptosis, which are central to conditions like Alzheimer's and Parkinson's disease. This review explores the complex relationship between NO and ROS in disease mechanisms, emphasizing cutting-edge therapeutic strategies that utilize redox signaling in cardiovascular and neurological conditions.},
}

Humans
*Reactive Oxygen Species/metabolism
*Nitric Oxide/metabolism
*Signal Transduction/physiology
Oxidation-Reduction
*Brain/metabolism
Animals
Oxidative Stress/physiology
*Myocardium/metabolism
Antioxidants/therapeutic use
Cardiovascular Diseases/metabolism

@article {pmid41603986,
year = {2026},
author = {Bozkır, İ and İbişoğlu, MS and Kayıkçıoğlu Bozkır, İ and Güler, Hİ},
title = {Computational prioritization of multi-target inhibitors: explainable QSAR and docking-based discovery of dual AChE/BACE1 chemotypes.},
journal = {Journal of computer-aided molecular design},
volume = {40},
number = {1},
pages = {54},
pmid = {41603986},
issn = {1573-4951},
mesh = {*Amyloid Precursor Protein Secretases/antagonists & inhibitors/chemistry/metabolism ; Quantitative Structure-Activity Relationship ; Molecular Docking Simulation ; *Aspartic Acid Endopeptidases/antagonists & inhibitors/chemistry ; *Acetylcholinesterase/chemistry/metabolism ; *Cholinesterase Inhibitors/chemistry/pharmacology ; Humans ; Drug Discovery ; },
abstract = {The discovery of dual acetylcholinesterase (AChE) and β-secretase (BACE1) inhibitors remains a promising strategy against multifactorial Alzheimer's disease. Here, rigorously curated ChEMBL-derived data were used to develop explainable QSAR (Quantitative structure-activity relationship) models for dual-inhibition prioritization. Molecules were standardized, near-duplicates were removed using a Tanimoto similarity threshold (≥ 0.80), and physicochemical outliers were filtered prior to modeling. Multiple classifiers (including Light Gradient-Boosting Machine, eXtreme Gradient Boosting, Random Forest, Support Vector Machine, k-Nearest Neighbors and Gradient Boosting Decision Trees) and fingerprints (e.g., RDKit fingerprints, Extended Connectivity Fingerprint) were benchmarked under scaffold-based nested cross-validation to prevent data leakage. Class imbalance was handled with SMOTETomek applied strictly within training folds. Model selection relied on F-Score, Area Under the Precision-Recall Curve, Matthews Correlation Coefficient (MCC), and Recall, and performance was accompanied by bootstrap confidence intervals, calibration curves, and Y-randomization controls. In classification, the top model (GBDT + ECFP6) achieved strong generalization (Recall ≈ 1.00, PR-AUC ≈ 0.84, MCC ≈ 0.81, F1 Score ≈ 0.84). Shapley Additive Explanations (SHAP) analysis highlighted aromatic and hydrogen-bonding substructures as key positive contributors. Prospective candidates (e.g., CHEMBL5082250, CHEMBL1651126, CHEMBL1651127) were evaluated by active-site-focused docking against AChE (PDB: 4EY7) and BACE1 (PDB: 2G94) with essential waters retained; docking scores (ΔG, kcal·mol[-][1]) were used for relative ranking of the ligands. SwissADME/pkCSM profiling suggested CNS-relevant properties (e.g., MPO, logBB, P-gp liability) and acceptable oral drug-likeness. Collectively, the workflow provides a reproducible and transparent pipeline for prioritizing dual AChE/BACE1 chemotypes and nominates testable scaffolds for experimental validation.},
}

*Amyloid Precursor Protein Secretases/antagonists & inhibitors/chemistry/metabolism
Quantitative Structure-Activity Relationship
Molecular Docking Simulation
*Aspartic Acid Endopeptidases/antagonists & inhibitors/chemistry
*Acetylcholinesterase/chemistry/metabolism
*Cholinesterase Inhibitors/chemistry/pharmacology
Humans
Drug Discovery

@article {pmid41603947,
year = {2026},
author = {Dang, M and Chen, K and Wang, D and Sang, F and Zhang, Z and Chen, Y and , },
title = {Stage-specific temporal associations between body mass index trajectories and Alzheimer's disease pathologies.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {41603947},
issn = {1432-1084},
support = {2023YFC3605400//National Key Research and Development Program of China/ ; 2022ZD0211600//Science and Technology Innovation 2030 Major Projects/ ; GZC20252268//Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation/ ; CX202408//Joint Innovation Team for Clinical & Basic Research, Shandong First Medical University/ ; },
abstract = {OBJECTIVES: Preclinical declines in body mass index (BMI) are linked to accelerated Alzheimer's disease (AD) neurodegeneration and mortality, yet the temporal relationship between premorbid BMI trajectories and AD neuropathology remains unclear. This study aims to characterize stage-specific BMI dynamics preceding mild cognitive impairment (MCI)/AD diagnosis and evaluate their bidirectional associations with core AD pathologies.

MATERIALS AND METHODS: This longitudinal cohort study analyzed 1570 participants (mean age 73.2 ± 6.9 years; 53% male) from the Alzheimer's Disease Neuroimaging Initiative, applied linear mixed-effect models to construct BMI trajectories, and used partial correlation analysis and cross-lagged panel model to assess bidirectional associations between BMI changes and pathological progression, including β-amyloid (Aβ), tau, and neurodegeneration.

RESULTS: Frontotemporal Aβ deposition preceded and predicted preclinical BMI decline (β = -5.74, p = 0.003), which subsequently correlated with accelerated neurodegeneration during MCI transition, including hypometabolism (r = 0.42, p < 0.001) and gray matter atrophy (r = 0.24, p = 0.01). Post-MCI diagnosis, BMI trajectories stabilized, yet lower BMI was associated with elevated cerebrospinal fluid tau levels, regardless of AD conversion. Importantly, lower premorbid BMI at MCI diagnosis was linked to faster temporo-occipital tau accumulation (r = -0.53, p = 0.01) and temporal hypometabolism (r = 0.23, p = 0.002) during MCI-to-AD progression.

CONCLUSIONS: This study suggests a temporal relationship between BMI trajectories and AD pathology: early Aβ deposition predicts preclinical BMI decline, which exacerbates tauopathy and neurodegeneration. These findings reveal a self-reinforcing cycle wherein BMI decline reflects incipient pathology and amplifies disease progression through stage-specific mechanisms.

KEY POINTS: Question What is the association between changes in body mass index (BMI) and the pathological progression of Alzheimer's disease? Findings Early frontotemporal β-amyloid deposition predicts preclinical BMI decline, which in turn is associated with accelerated tau accumulation and neurodegeneration during symptomatic progression. Clinical relevance Monitoring BMI trajectories provides a low-cost approach to identifying individuals at high risk for Alzheimer's disease and tracking its pathological progression, highlighting the potential value of metabolic interventions during preclinical stages.},
}

@article {pmid41603883,
year = {2026},
author = {Burn, O and Molloy, K and Kanekiyo, M and Parker, C and Rothwell, S and Pan, JJ and Trueman, D and Ritchie, C},
title = {Estimating the long-term health outcomes of treatment with lecanemab in early Alzheimer's disease: a modelling study.},
journal = {Journal of medical economics},
volume = {29},
number = {1},
pages = {250-262},
doi = {10.1080/13696998.2025.2600875},
pmid = {41603883},
issn = {1941-837X},
mesh = {Humans ; *Alzheimer Disease/drug therapy ; Markov Chains ; Aged ; Male ; Female ; Severity of Illness Index ; Cognitive Dysfunction/drug therapy ; Aged, 80 and over ; Standard of Care ; Disease Progression ; Quality-Adjusted Life Years ; },
abstract = {AIMS: To assess the long-term effects of lecanemab plus standard of care (SoC) compared with SoC alone in a cohort of patients with early Alzheimer's disease (AD; mild cognitive impairment [MCI] due to AD, or mild AD dementia) using different modeling approaches and data from Clarity AD (NCT0388745538).

METHODS: A Markov model was employed using health states based on disease severity, long-term institutionalization, and death, with disease severity defined using the Clinical Dementia Rating - Sum of Boxes (CDR-SB) classification for MCI due to AD, and Mild, Moderate, and Severe AD. State transitions during the first 18 months of treatment were estimated using either patient count data (Approach 1) or multistate survival analysis (Approach 2). Transition probabilities beyond 18 months for the lifetime of the cohort were informed by longitudinal natural history data for the SoC arm with a hazard ratio for time-to-worsening health state applied to estimate outcomes in the lecanemab arm.

RESULTS: Over a lifetime horizon, the model predicted a delayed time to Mild, Moderate, and Severe AD for patients treated with lecanemab compared to SoC by 1.31, 1.85, and 2.04 years, respectively when using Approach 1. Patients treated with lecanemab experienced a survival benefit of 1.36 years, comprised of an additional 1.85 years in early AD and 0.49 years less in moderate and severe AD, compared to patients treated with SoC alone. The model also predicted that compared to SoC, lecanemab increased the time in community care and reduced time spent in institutional care. Results were similar when using Approach 2.

LIMITATIONS: Long-term disease progression was informed by constant annual transition probabilities derived from the published literature.

CONCLUSIONS: Patients treated with lecanemab experience delayed progression to Moderate and Severe AD, resulting in additional life-years (LYs) and reduced time in institutional care.},
}

Humans
*Alzheimer Disease/drug therapy
Markov Chains
Aged
Male
Female
Severity of Illness Index
Cognitive Dysfunction/drug therapy
Aged, 80 and over
Standard of Care
Disease Progression
Quality-Adjusted Life Years

@article {pmid41603647,
year = {2026},
author = {Duong, MT and Das, SR and Khandelwal, P and Vizcarra, JA and Li, Y and Xie, L and Yushkevich, PA and Shaw, LM and Dubroff, JG and , and Siderowf, A and Wolk, DA and Nasrallah, IM},
title = {Discordance of Dopaminergic Dysfunction and Subcortical Atrophy by α-Synuclein Status in Sporadic and Genetic Parkinson's Disease.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.70186},
pmid = {41603647},
issn = {1531-8257},
support = {F30-AG074524//National Institutes of Health (NIH)/ ; T32-NS091006-10//National Institutes of Health (NIH)/ ; R01-AG072796//National Institutes of Health (NIH)/ ; UL1-TR001878//Institute for Translational Medicine and Therapeutics pilot/ ; P30-AG072979//Alzheimer's Disease Core Center/ ; //Michael J. Fox Foundation/ ; },
abstract = {BACKGROUND: Parkinson's disease (PD) is characterized by predominantly neuronal α-synuclein pathology and dopaminergic dysfunction. Cerebrospinal fluid (CSF) seeding amplification assays (SAA) detect α-synuclein aggregates in vivo, but not all patients with PD have a positive SAA. This pathological heterogeneity among patients may not be entirely captured by binary results from α-synuclein SAA positivity (S+) versus negativity (S-). To further dissect this biological variability, we explored spatial neuroimaging differences in S+ versus S- patients.

OBJECTIVE: The study aim was to investigate how SAA status influences imaging measures of dopamine denervation and atrophy.

METHODS: We compare SAA status with CSF proteinopathy markers, [123]I-Ioflupane dopamine transporter (DAT), and magnetic resonance imaging (MRI) in participants with sporadic (n = 490), LRRK2-associated (n = 158), and GBA-associated (n = 80) PD from the Parkinson's Progression Markers Initiative (PPMI).

RESULTS: Between 64% and 95% of participants in these groups have S+ status. For all groups, S+ participants have decreased putamen DAT neurotransmission compared to S- participants, whereas S- participants have reduced MRI volume in basal ganglia structures relative to S+ participants. With striatal DAT/MRI ratios, S+ participants have disproportionately lower putamen DAT uptake relative to atrophy. In exploratory analyses, participants with cognitive impairment or hyposmia are associated with worse DAT/MRI discordance. By CSF markers, S- participants with sporadic PD have higher CSF pTau181/amyloid-β42 ratio, suggesting Alzheimer's copathology.

CONCLUSIONS: S+ patients exhibit more dopaminergic deficit, whereas S- patients have more subcortical atrophy across sporadic and genetic PD. Together, our findings reveal structure/function and DAT/MRI discordance, providing insight into biomarkers and pathophysiology of synucleinopathy and PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}

@article {pmid41603464,
year = {2026},
author = {Jacobs, HIL},
title = {The monoaminergic systems as drivers of Alzheimer's disease pathophysiology and symptomatology.},
journal = {Current opinion in neurology},
volume = {},
number = {},
pages = {},
pmid = {41603464},
issn = {1473-6551},
abstract = {PURPOSE OF REVIEW: To summarize recent animal, postmortem and in vivo human studies examining the role of the noradrenergic and serotonergic system in the pathophysiology and symptomatology of Alzheimer's disease (AD).

RECENT FINDINGS: Early in adulthood, the locus coeruleus and raphe nucleus accumulate tau, undergo morphological changes, and exhibit hyperexcitability, which contributes to the development of neuropsychiatric symptoms. As cortical AD pathology increases, these nuclei become hypoactive, but elevated neurotransmitter levels persist in the cortex, presumably driving amyloid-related hyperexcitability and contributing to tau spreading and cognitive decline.

SUMMARY: The pathologic changes occurring within these monoaminergic systems temporally align with the observation that neuropsychiatric symptoms precede cognitive changes in AD, indicating that these systems link the earliest pathobiology of the disease to the evolution of the symptoms. The proposed monoaminergic framework intends to guide researchers into investigating the temporal dynamics between monoaminergic changes, AD pathology, and symptoms, with the ultimate goal of evaluating and developing effective precision therapeutic approaches taking into account the disease stage and symptom profile.},
}

@article {pmid41603414,
year = {2026},
author = {Libby, JB and Deters, KD and Ertekin-Taner, N and Carrasquillo, MM and Allen, M and De Jager, P and Menon, V and Zhang, B and Haroutunian, V and Levey, AI and Seyfried, NT and Kaddurah-Daouk, R and Finkbeiner, S and Wang, D and Greenwood, AK and Vander Linden, A and Heath, L and Poehlman, WL and Dumitrescu, L and Petyuk, VA and Bennett, DA and Schneider, JA and Barnes, LL and Hohman, TJ},
title = {Multi-omic expression of the VEGF family relates to Alzheimer's disease across diverse populations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {1},
pages = {e71100},
doi = {10.1002/alz.71100},
pmid = {41603414},
issn = {1552-5279},
support = {U01AG046139/GF/NIH HHS/United States ; U01AG046170/GF/NIH HHS/United States ; U01AG061357/GF/NIH HHS/United States ; U01AG061356/GF/NIH HHS/United States ; U01AG061359/GF/NIH HHS/United States ; R01AG067025/GF/NIH HHS/United States ; R01AG061518/GF/NIH HHS/United States ; U19AG063744/GF/NIH HHS/United States ; U19AG063744-04S1/GF/NIH HHS/United States ; U01AG024904-09S4/GF/NIH HHS/United States ; R01AG046171/GF/NIH HHS/United States ; RF1AG059093/GF/NIH HHS/United States ; RF1AG058942/GF/NIH HHS/United States ; RF1AG051550/GF/NIH HHS/United States ; P30AG10161/GF/NIH HHS/United States ; P30AG72975/GF/NIH HHS/United States ; R01AG15819/GF/NIH HHS/United States ; R01AG17917/GF/NIH HHS/United States ; U01AG46152/GF/NIH HHS/United States ; U01AG61356/GF/NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/genetics/metabolism/pathology ; Male ; Female ; Aged ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; *Brain/pathology/metabolism ; Proteomics ; Aged, 80 and over ; White People ; Multiomics ; },
abstract = {INTRODUCTION: The vascular endothelial growth factor (VEGF) signaling family plays a role in neurodegenerative diseases, including Alzheimer's disease (AD). Previous work has shown widespread effects of the members FLT1, FLT4, and VEGFB on AD outcomes. However, these analyses have focused within the non-Hispanic White (NHW) population.

NETHODS: The goal of this study was to analyze the effects of the VEGF family in underrepresented populations, leveraging large and diverse bulk RNA sequencing and tandem mass tag-mass spectrometry (TMT-MS) proteomic data. Outcomes included measures of AD pathology and diagnosis.

RESULTS: Within underrepresented populations, we replicated previously reported effects of FLT1 and FLT4, whereby higher protein abundance was observed in the AD brain and was associated with higher neuropathology burden. In stratified analyses, these associations were largely consistent across race and ethnicity.

DISCUSSION: This multi-omic study on the role of the VEGF family in AD emphasizes the need for more representative studies focused on therapeutic targets for AD.

HIGHLIGHTS: Vascular endothelial growth factor (VEGF) genes and proteins were quantified in four different brain regions. Samples included participants from four different populations. Previously observed effects were replicated in diverse populations. This study is the largest multi-omic study of the vascular endothelial growth factor (VEGF) genes among Alzheimer's disease (AD) participants from diverse populations.},
}

Humans
*Alzheimer Disease/genetics/metabolism/pathology
Male
Female
Aged
*Vascular Endothelial Growth Factor A/metabolism/genetics
*Brain/pathology/metabolism
Proteomics
Aged, 80 and over
White People
Multiomics

@article {pmid41603393,
year = {2026},
author = {Andrews, SC and Eramudugolla, R and Sinclair, C and Mortby, ME and Cherbuin, N and Anstey, KJ},
title = {Neuropsychological subtypes of incident mild cognitive impairment and mild neurocognitive disorder in a population-based cohort of older adults.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251415023},
doi = {10.1177/13872877251415023},
pmid = {41603393},
issn = {1875-8908},
abstract = {BackgroundMild cognitive impairment (MCI) is a heterogenous condition which places individuals at higher risk for Alzheimer's disease, yet it is not well understood. Studies of primarily prevalent MCI have identified different subtypes characterized by different neuropsychological profiles, while a recent incident MCI study empirically identified four neuropsychological subtypes (amnestic, dysexecutive, dysnomic, and subtle cognitive impairment (SCI) subtypes).ObjectiveWe aimed to identify whether four distinct neuropsychological subtypes could be empirically derived in a sample of a) incident MCI and b) DSM5 mild neurocognitive disorder (mNCD).MethodsWe used data from the Personality and Total Health Through Life study. Participants were aged 72-78, with a diagnosis of incident MCI (n = 117), and/or mNCD (n = 161). We undertook a cross-sectional cluster analysis on neuropsychological data from participants from four domains: executive, memory, language, and visuospatial.ResultsFor incident MCI, cluster analysis derived four subtypes, (dysexecutive, SCI, mixed dysnomic/visuospatial and mixed dysexecutive/visuospatial). For mNCD, the resulting four cluster solution included dysexecutive, SCI-amnestic/dysnomic, SCI-dysexecutive and mixed/global impairment. Discriminant function analysis revealed that 94% and 91% of MCI and mNCD participants respectively were correctly classified based on the cognitive domain scores, and further analysis confirmed the SCI groups showed reduced cognitive performance compared with matched cognitively unimpaired participants.ConclusionsNeuropsychological subtypes were empirically derived in both incident MCI and mild NCD samples, with both SCI and dysexecutive clusters most reliably detected and consistent with previous studies. The early identification of these MCI/mNCD subtypes may help to identify patient groups for targeted early intervention in clinical settings.},
}

@article {pmid41603392,
year = {2026},
author = {Prevot, E and Shand, C and , and Oxtoby, N},
title = {How reproducible are data-driven subtypes of Alzheimer's disease atrophy?.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251415019},
doi = {10.1177/13872877251415019},
pmid = {41603392},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) exhibits substantial clinical and biological heterogeneity, complicating efforts in treatment and intervention development. While new computational methods offer insights into AD subtyping and disease staging, the reproducibility of these subtypes across datasets remains understudied, particularly concerning the robustness of subtype definitions when validated on diverse databases.ObjectiveThis study evaluates the robustness of the AD progression subtypes identified by the Subtype and Stage Inference (SuStaIn) algorithm on a larger and more diverse cohort.MethodsWe extracted T1-weighted MRI data for 5444 subjects from ANMerge, OASIS, and ADNI datasets, forming four independent cohorts. Each cohort was analyzed with SuStaIn under two conditions: one using the full cohort, including cognitively normal controls, and another excluding controls to test subtype robustness.ResultsResults confirm the three primary atrophy subtypes identified in earlier studies: Typical, Cortical, and Subcortical, as well as the emergence of rare and atypical AD variants such as posterior cortical atrophy. Notably, each subtype displayed varying robustness to the inclusion of controls, with certain subtypes, like the Subcortical subtype, more influenced by cohort composition.ConclusionsThis investigation underscores SuStaIn's reliability for defining stable AD subtypes and suggests its utility in clinical stratification for trials and diagnosis. However, our findings also highlight the need for improved dataset ethnic and demographic diversity, particularly in terms of ethnic representation, to enhance generalizability and support broader clinical application.},
}

@article {pmid41603391,
year = {2026},
author = {Housini, M and Contreras, JA and Hayes, CA and , },
title = {Independent associations of phosphorylated tau181 and neurofilament light with cognitive outcomes in the Health and Aging Brain Study-Health Disparities (HABS-HD).},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251415367},
doi = {10.1177/13872877251415367},
pmid = {41603391},
issn = {1875-8908},
abstract = {BackgroundThe extent to which plasma biomarkers of Alzheimer's disease and neurodegeneration capture domain-specific cognitive performance across diverse populations remains unclear.ObjectiveTo determine whether plasma phosphorylated tau181 (p-tau181) and neurofilament light (NfL) are independently associated with cognitive domains, and whether associations differ across non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic participants.MethodsWe analyzed 3023 community-dwelling older adults from the Health and Aging Brain Study-Health Disparities (38.4% NHW, 22.6% NHW, 38.9% Hispanic). We used linear regressions to test associations between plasma biomarkers and cognitive domains (memory, executive function, processing speed, language), adjusting for age, sex, education, and apolipoprotein ε4 carriership. We fit models including both p-tau181 and NfL to assess their independent associations, evaluate biomarker × racial/ethnic interactions, and test p-tau181 × NfL interactions within each racial/ethnic group.ResultsAmong NHW participants, higher p-tau181 and NfL were associated with poorer memory, executive function, processing speed, and language. In NHB participants, p-tau181 was associated with memory, showed attenuated associations for language, and demonstrated similar associations with executive function and processing speed as observed in NHW participants. In Hispanic participants, p-tau181 was associated with memory and processing speed but was nonsignificant for executive function and language, and NfL showed significant but attenuated associations across all domains. Higher p-tau181 and NfL were jointly associated with slower processing speed only in NHW and NHB participants.ConclusionsPlasma p-tau181 and NfL were associated with multiple cognitive domains, with the strongest effects in NHW participants and attenuated associations in NHB and Hispanic individuals.},
}