Journal of Alzheimer's Disease最新文献

{"title":"Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers.","authors":"Alzbeta Katonova, Ross Andel, Vanesa Jurasova, Katerina Veverova, Francesco Angelucci, Vaclav Matoska, Jakub Hort","doi":"10.1177/13872877251326199","DOIUrl":"https://doi.org/10.1177/13872877251326199","url":null,"abstract":"<p><p>Background<i>KLOTHO</i>-VS heterozygosity (<i>KL</i>-VSHET) and soluble α-Klotho (sαKl) protein interfere with Alzheimer's disease (AD) pathophysiology, but the specific relationships remain unclear. This study explored these associations across the AD continuum, focusing on core AD biomarkers and markers of neurodegeneration, neuroinflammation, and synaptic dysfunction.ObjectiveWe investigated whether 1) <i>KL</i>-VSHET is associated with lower AD biomarker burden (Aβ₄₂, Aβ_42/40 ratio, P-tau181, T-tau) and neurodegeneration (NfL); 2) sαKl relates to AD biomarkers, neurodegeneration (NfL), neuroinflammation (GFAP), and synaptic dysfunction (Ng); 3) associations vary by <i>APOE</i> ε4 status and clinical subgroup.MethodsParticipants (n = 223) were categorized as cognitively healthy (n = 38), aMCI-AD (n = 94), and AD dementia (n = 91). <i>KLOTHO</i> genotyping was available for 128 participants; 138 had cerebrospinal fluid (CSF) and serum sαKl measurements; and 42 had both. Multiple linear regression evaluated associations between <i>KL</i>-VSHET, sαKl levels, and biomarkers, stratified by <i>APOE</i> ε4 status and clinical subgroup.ResultsOverall, the associations between <i>KL</i>-VSHET and higher CSF Aβ₄₂ and Aβ_42/40 ratio were non-significant (<i>p</i>s ≥ 0.059) except when restricted to <i>APOE</i> ε4 carriers only (β = 0.11, <i>p </i>= 0.008 and β = 0.16, <i>p </i>= 0.033, respectively). Within clinical subgroups, <i>KL</i>-VSHET was positively associated with Aβ_42/40 ratio only in aMCI-AD (β = 0.23, <i>p </i>= 0.034). No significant associations were observed between <i>KL</i>-VSHET and tau biomarkers or NfL. For sαKl, associations with biomarkers were non-significant except for a negative association of serum sαKl with P-tau181 in aMCI-AD (β = -0.25, p = 0.036) and a positive association with Aβ_42/40 ratio in <i>APOE</i> ε4 non-carriers (β = 0.24 p = 0.047).Conclusions<i>KL</i>-VSHET may help protect against amyloid pathology, particularly in the presence of <i>APOE</i> ε4, and regardless of <i>APOE</i> status in aMCI-AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251326199"},"PeriodicalIF":3.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying microglia-derived NFKBIA as a potential contributor to the pathogenesis of Alzheimer's disease and age-related macular degeneration.","authors":"Shizhen Lei, Yani Liu","doi":"10.1177/13872877251326267","DOIUrl":"https://doi.org/10.1177/13872877251326267","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) place considerable health burden on affected individuals and significant economic burden on society.ObjectiveThis study aims to explore the shared cellular and molecular mechanisms underlying the pathogenesis of AD and AMD.MethodsThe investigation in this study is conducted via single-cell and bulk tissue transcriptomic analysis. Transcriptomic datasets of AD and AMD were obtained from the GEO database. The shared differentially expressed genes (DEGs) in control and AD- and AMD-affected samples were identified. Functional enrichment analysis for DEGs was subsequently performed. Then, the protein-protein interaction (PPI) network of these DEGs was established via the STRING database and hub genes of this network were identified by Cytoscape software. Single-cell transcriptomic analysis was performed using Seurat R package to explore their expression in different cell types.ResultsDifferential analysis identified 127 shared DEGs of the two diseases, including 71 upregulated and 56 downregulated genes. Upregulated DEGs were enriched in inflammation, gliogenesis, cell apoptosis, and response to bacterial and viral infection and downregulated DEGs were enriched in mitochondrial function and energy production. PPI network and Cytoscape determined 10 hub genes, of which the NFKBIA gene was associated with the severity of both AD and AMD. Moreover, single-cell transcriptomic analysis showed that NFKBIA was highly expressed in microglia from disease-affected tissues.ConclusionsThe findings indicated that microglia with high NFKBIA expression were important contributors to the progression of both AD and AMD. Microglia-derived NFKBIA might serve as a potential therapeutic target for AD and AMD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251326267"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid LMO4 as a synaptic biomarker linked to Alzheimer's disease pathology and cognitive decline.","authors":"Yu-Han Chen, Zhi-Bo Wang, Xi-Peng Liu, Zhi-Qi Mao","doi":"10.1177/13872877251326286","DOIUrl":"https://doi.org/10.1177/13872877251326286","url":null,"abstract":"<p><p>BackgroundLIM-domain-only 4 (LMO4) is involved in neurodevelopment and synaptic plasticity, but its role in the pathogenesis of Alzheimer's disease (AD) remains unclear.ObjectiveTo investigate the association between cerebrospinal fluid (CSF) LMO4 levels and core AD biomarkers, neurodegeneration, and cognitive decline.MethodsWe included 703 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Associations between CSF LMO4 and AD biomarkers (Aβ₄₂, Ptau181, amyloid PET) and postmortem neuropathology were evaluated. We also explored cross-sectional and longitudinal associations between CSF LMO4 and neurodegeneration and cognitive function. Receiver operating characteristic (ROC) analysis assessed the diagnostic accuracy of CSF LMO4 in distinguishing Aβ-positive from Aβ-negative participants and amyloid PET-confirmed AD cases. Mediation analysis explored the potential mediating role of CSF LMO4 between Aβ pathology and tau pathology.ResultsLMO4 levels were decreased in participants with abnormal Aβ levels and cognitive impairment. Lower CSF LMO4 levels were associated with increased Aβ and tau pathology, brain atrophy, cognitive decline, and postmortem neuropathology. CSF LMO4 partially mediated the relationship between Aβ and tau pathology and demonstrated acceptable discriminative ability in distinguishing Aβ-positive from Aβ-negative participants and amyloid PET-confirmed AD from non-AD cases.ConclusionsCSF LMO4 plays a crucial role in the pathogenesis and progression of AD and may represent a potential therapeutic target for AD treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251326286"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEG biomarkers for Alzheimer's disease: A novel automated pipeline for detecting and monitoring disease progression.","authors":"Leif Er Simmatis, Emma E Russo, Tayo Steininger, Haleigh Riddell, Evelyn Chen, Queenny Chiu, Michelle Lin, Donghun Oh, Porsha Taheri, Irene E Harmsen, Nardin Samuel","doi":"10.1177/13872877251327754","DOIUrl":"https://doi.org/10.1177/13872877251327754","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder that profoundly alters brain function and organization. Currently, there is a lack of validated functional biomarkers to aid in diagnosing and classifying AD. Therefore, there is a pressing need for early, accurate, non-invasive, and accessible methods to detect and characterize disease progression. Electroencephalography (EEG) has emerged as a minimally invasive technique to quantify functional changes in neural activity associated with AD. However, challenges such as poor signal-to-noise ratio-particularly for resting-state (rsEEG) recordings-and issues with standardization have hindered its broader application.ObjectiveTo conduct a pilot analysis of our custom automated preprocessing and feature extraction pipeline to identify indicators of AD and correlates of disease progression.MethodsWe analyzed data from 36 individuals with AD and 29 healthy participants recorded using a standard 19-channel EEG and features were processed using our custom end-t-end pipeline. Various features encompassing amplitude, power, connectivity, complexity, and microstates were extracted. Unsupervised machine learning (uniform manifold approximation and projection) and supervised learning (random forest classifiers with nested cross-validation) were used to characterize the dataset and identify differences between AD and healthy groups.ResultsOur pipeline successfully detected several new and previously established EEG-based measures indicative of AD status and progression, demonstrating strong external validity.ConclusionsOur findings suggest that this automated approach provides a promising initial framework for implementing EEG biomarkers in the AD patient population, paving the way for improved diagnostic and monitoring strategies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251327754"},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated circulating cathepsin S levels are associated with cognitive decline and neurodegeneration in a cohort of patients reporting memory complaints.","authors":"Jian Wang, Duo-Zi Wang, Bing-Hu Li, Shu Yang, Fu-Qiang Guo, Bo Zheng, Jian-Hong Wang","doi":"10.1177/13872877251322809","DOIUrl":"https://doi.org/10.1177/13872877251322809","url":null,"abstract":"<p><p>BackgroundAs a member of the cysteine protease family, cathepsin S has been implicated in the pathogenesis of various diseases, including Alzheimer's disease (AD), primarily by promoting inflammation.ObjectiveCurrent evidence regarding the role of cathepsin S primarily comes from animal studies. This study aims to explore the clinical relevance of cathepsin S in AD.MethodsIn a cohort of older adults aged 60 or above with memory complaints, we examined baseline plasma levels of cathepsin S and assessed their association with cognitive decline and biomarkers of neurodegeneration during a 36-month follow-up.ResultsPlasma levels of cathepsin S were significantly higher in individuals experiencing longitudinal cognitive decline compared to those without cognitive decline. Furthermore, plasma levels of cathepsin S were associated with declines in Mini-Mental State Examination (MMSE) scores and increases in neurofilament light and pTau181 levels. Higher plasma cathepsin S levels were linked to an increased risk of longitudinal cognitive decline (decrease in MMSE scores of 3 or more), adjusting for age, sex, education, <i>APOE</i> genotype, alcohol consumption, smoking, and comorbidities.ConclusionsThis study provides additional evidence supporting the potential role of cathepsin S in the pathogenesis of AD from a clinical perspective.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251322809"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid VGF is associated with the onset and progression of Alzheimer's disease.","authors":"Yuanyuan Lu, Dan Li, Yueyi Yu, Qianqian Wang, Aonan Li, Yixin Quan, Yi Xing","doi":"10.1177/13872877251323002","DOIUrl":"https://doi.org/10.1177/13872877251323002","url":null,"abstract":"<p><p>BackgroundIt remains unclear whether cerebrospinal fluid (CSF) VGF (non-acronymic) is associated with the onset and progression of Alzheimer's disease (AD).ObjectiveTo assess the levels of CSF VGF throughout the AD continuum, and its association with primary AD pathology, cognition, brain atrophy, and brain metabolism.MethodsWe studied a total of 526 individuals including 377 amyloid-positive individuals (76 preclinical AD, 200 prodromal AD, and 101 AD dementia) and 149 amyloid-negative cognitively normal individuals. VGF peptide in CSF was analyzed using mass spectrometry.ResultsWe observed decreased CSF VGF in preclinical, prodromal, and AD dementia individuals than amyloid-negative cognitively normal individuals. Reduced CSF VGF was associated with cognitive decline, hippocampal atrophy, ventricle enlargement, and glucose hypometabolism at baseline, and it predicted a more marked deterioration over time.ConclusionsOur findings support the important contributions of VGF to disease pathogenesis and progression in the early stages of AD. Exploring the biologics modulating VGF might be a promising approach for AD prevention and early treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251323002"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of subclinical depressive and anxiety symptoms in older adults with subjective cognitive decline progressing to objective cognitive impairment: A prospective 4-year follow-up study.","authors":"Béatrice Raymond-Lessard, Claude Bélanger, Carol Hudon, Sébastien Grenier","doi":"10.1177/13872877251319538","DOIUrl":"https://doi.org/10.1177/13872877251319538","url":null,"abstract":"<p><p>BackgroundSubjective cognitive decline (SCD) is linked to a more rapid progression to the development of mild cognitive impairment (MCI) or Alzheimer's disease (AD). SCD has been correlated with affective symptoms such as depression and anxiety. Recent research aimed to shed light on the relationship between these affective symptoms and how they might correlate to a more rapid progression to objective cognitive impairment. No studies have assessed the presence, type, and intensity of depressive and anxiety symptoms between SCD individuals who progressed versus those who did not.ObjectiveThis study aimed to establish whether there are differences between subclinical depressive and anxiety symptoms in terms of presence, type, and intensity of symptoms presented by individuals with SCD who progressed to an objective cognitive decline.MethodsThe recruited participants originated from the Consortium for the Early Identification of Alzheimer's Disease - Québec (CIMA-Q) cohort. They were assessed twice, with an interval of 4 years separating the evaluations. Anxiety symptoms were assessed using the Geriatric Anxiety Inventory (GAI) and depression symptoms using the Geriatric Depression Scale (GDS-30).ResultsThe presence, type and intensity of anxiety symptoms did not significantly distinguish the two groups. Only one type of hopelessness-related depressive symptom was significantly higher in SCD participants who had progressed to objective cognitive decline compared with those who had not.ConclusionsOur results suggest that it may be beneficial to target hopelessness in non-pharmacological interventions aimed at preventing the progression of people with SCD to MCI or AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251319538"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of the Chinese Naming Test (CNT): Diagnostic efficacy and correlation with Alzheimer's disease biomarkers.","authors":"Zhen Zhang, Liang Cui, Lin Huang, Yi-Hui Guan, Fang Xie, Qi-Hao Guo","doi":"10.1177/13872877251324100","DOIUrl":"https://doi.org/10.1177/13872877251324100","url":null,"abstract":"<p><p>BackgroundNeuropsychological assessments are essential tools for the screening and diagnosis of patients with cognitive impairments. Cultural background differences significantly affect cognitive test performance. For China, which is rapidly aging, a culturally adaptive picture naming test is urgently needed.ObjectiveThis study aims to develop a Chinese naming test (CNT) adapted to the cultural background of Chinese people and to explore its correlation with Alzheimer's disease (AD) biomarkers.MethodsA total of 1459 participants were recruited, including 744 with normal cognition (NC), 492 with mild cognitive impairment (MCI), and 223 with dementia. All participants underwent a comprehensive neuropsychological assessment. The diagnostic capability of CNT was determined using Receiver Operating Characteristic curves. Part of participants underwent amyloid-β (Aβ) PET scans, tau-PET scans, and MRI scans. The relationships between CNT scores and Aβ and tau deposition, as well as brain structural changes, were analyzed.ResultsThe diagnostic capability of CNT for MCI showed a sensitivity of 68.7%, specificity of 75.6%, and AUC of 0.81; for dementia, the sensitivity was 72.7%, specificity was 89.5%, and AUC was 0.89. The correlation coefficient between CNT scores and brain Aβ burden was -0.11 (p = 0.024). CNT scores correlated with tau burden in different Braak stages (p < 0.05). The correlation coefficient between CNT scores and hippocampus atrophy was -0.15 (p = 0.003).ConclusionsThe CNT has good diagnostic performance in detecting MCI and dementia in Chinese population. There is a correlation between CNT scores and AD imaging markers, indicating that the CNT might has potential value in predicting cognitive changes and disease progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251324100"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dementia diagnosis and prescription of antidementia drugs: An analysis of German claims data (2006-2016).","authors":"Cornelia Becker, Lucas Herschung, Willy Gomm, Britta Haenisch","doi":"10.1177/13872877251319468","DOIUrl":"https://doi.org/10.1177/13872877251319468","url":null,"abstract":"<p><p>BackgroundUse of claims data allows to analyze health service characteristics of dementia, which is one of the most frequent cognitive disorders in Germany and worldwide.ObjectiveThe study aimed at describing the variability in dementia diagnoses and in antidementia drug prescription pattern.MethodsWe analyzed data from a population-based sample of one of the largest German statutory health insurances. The cohort included 30,403 patients with incident dementia diagnosis from 2006-2016. We described frequencies, patterns, and interrelations of diagnoses (Alzheimer's disease (AD), vascular dementia, other specific dementia, unspecified dementia (UD), antidementia drugs (ADD), and professional groups. We described switches in diagnostic and medication patterns between index quarter and following quarters, and evaluated the prescriptions in relation to national guidelines.ResultsA total of 87% of patients received a diagnosis of UD in at least one quarter of insurance. In the quarter of incident diagnosis, 14% of patients received more than one diagnostic code of dementia, whereas over the course of observation, the majority of patients received more than one diagnostic code (61%). Most patients were diagnosed by a general practitioner without involving a specialist. All professional groups primarily made UD diagnoses except specialists who mainly diagnosed AD. Thirty-five percent of all patients and 67% of AD patients were prescribed an ADD at least once.ConclusionsSpecialists made the most specific diagnoses and prescribed most ADDs. A specialist consultation may be advisable, but only 34% of patients visited one. Many AD patients might be left untreated due to underdiagnosis or -treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251319468"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease.","authors":"Caroline J Zeiss, Anita Huttner, Angus C Nairn, Amy Arnsten, Dibyadeep Datta, Stephen M Strittmatter, Brent Vander Wyk, Alvaro Duque","doi":"10.1177/13872877251323787","DOIUrl":"10.1177/13872877251323787","url":null,"abstract":"<p><p>BackgroundAccurate placement of the macaque within the Alzheimer's disease (AD) research framework is essential to discover early-stage predictive biomarkers.ObjectiveTo assess utility of the aging macaque in advancing translational biomarker development for preclinical AD, we evaluated relative signal strength of comparable neuropathologic phenomena in macaques and patients.MethodsWe compared pathology in patient and macaque formalin-fixed paraffin embedded (FFPE) tissues using identical criteria. We quantified expression of amyloid-β (Aβ), pTau, and inflammatory and senescence markers across species. Distribution of AD-relevant markers were compared in FFPE and perfused frozen macaque brain to assess expression of labile proteins that could inform in-life fluid biomarkers.ResultsAβ pathology in macaques closely approximated patient pathology. Complex plaque composition in macaques implied significant disruption of synaptic connectivity. In FFPE tissue, pretangle pTau immunoreactivity placed the macaque in Braak Stage 1b. In perfused frozen tissue, soluble pTau distribution approximated Braak Stage III-IV. In macaque, Aβ, pTau, and acetylcholinesterase labeling co-localized to AD-vulnerable circuits. Significant association of glial fibrillary acidic protein with Aβ occurred in humans only. The senescence marker p16 correlated positively with pTau expression and negatively with Aβ in patients only. Macaques lacked neuropathologic co-morbidities.ConclusionsAD-relevant neuropathologic signals in the macaque support biomarker discovery in the areas of Aβ plaque evolution and associated synaptic disruption as well as early-stage tau phosphorylation. Relative protection from accumulation of senescence markers, fibrillar tau and neuropathologic co-morbidities in macaque implicate species difference in rates of biological brain aging. We provide over 4000 digital slides for further study.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251323787"},"PeriodicalIF":3.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}