Journal of Alzheimer's Disease最新文献

{"title":"Development and validation of machine learning models to predict risk of undiagnosed dementia using healthcare claims and electronic health record data.","authors":"Deborah E Barnes, Cynthia Benjamin, W John Boscardin","doi":"10.1177/13872877261474534","DOIUrl":"10.1177/13872877261474534","url":null,"abstract":"<p><p>BackgroundApproximately half of people living with Alzheimer's disease and related dementias are undiagnosed.ObjectiveTo develop and validate algorithms that predict risk of undiagnosed dementia using electronic health record (EHR) and/or healthcare claims data.MethodsStudy participants were adult patients aged 65 years or older without evidence of dementia (diagnosis/medication) at baseline in two U.S. data sources: 1) Medicare claims (2010 to 2021); 2) EHR and claims from a primary care network (2016 to 2023). We applied coefficients from an existing, validated EHR-based algorithm to predictors defined using Medicare claims and used machine learning to develop new EHR- and claims-based predictive models. We assessed model discrimination using c-statistics.ResultsStudy participants included 8,374,400 Medicare beneficiaries (mean [SD] age, 76 [7] years; 57% female) and 29,983 primary care patients (age: 75 [6] years; 56% female). Model discrimination was good when applying EHR-based coefficients to Medicare claims-based predictors (c-statistic [95% confidence interval]: 0.770 [0.767, 0.773]) and was improved by refitting the model (0.795 [0.792, 0.798]) with a small added benefit from incorporating new claims-based predictors (0.801 [0.799; 0.804]). Similarly, when both EHR and claims data were available, discrimination was improved by refitting the model with a small additional benefit from including new predictors, regardless of the data source (EHR, claims, or either).ConclusionsA validated EHR-based algorithm predicted risk of undiagnosed dementia in Medicare claims with good discrimination. Model accuracy was improved by refitting and, to a lesser extent, by including novel predictors.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261474534"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721485","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":"Lack of effect of repetitive mild traumatic brain injury early in life on the neuropathological and behavioral hallmarks of Alzheimer's disease in 3xTg-AD mice.","authors":"Casey C H Barker, Lilia A Koza, Lujain Almuhanna, Katelyn R Trujillo, Daniel A Linseman","doi":"10.1177/13872877261476274","DOIUrl":"10.1177/13872877261476274","url":null,"abstract":"<p><strong>Background: </strong>Repetitive traumatic brain injuries (rTBIs) are predicted to increase risk for neurodegenerative disorders including Alzheimer's disease (AD). <b>Objective:</b> By using a combination of behavioral tests and histopathology, we investigated whether brain trauma worsens cognitive dysfunction and brain pathology in 3xTg-AD mice subjected early in life to repetitive mild TBI (rmTBI). <b>Methods:</b> At 3 months old, mice in the rmTBI group were given 5 mTBIs, each separated by 48 h. Mice were aged to 10 months old and assessed for cognitive function using the Barnes maze and Novel Object Recognition behavioral tests. Hippocampal sections were stained for amyloid-β and phosphorylated-tau proteins that constitute pathological hallmarks of AD. Immunostaining for GFAP and Iba1 was also employed to assess glial reactivity in the hippocampus. <b>Results:</b> Results from the behavioral tests indicate that there are no significant differences in the severity of cognitive dysfunction between any of the 3xTg-AD mouse groups (naïve, SHAM, or rmTBI). As expected, wild-type mice perform better across all behavioral tests than any of the 3xTg-AD mice. Furthermore, we do not find any significant difference in the amount of amyloid-β aggregation, tau phosphorylation, or gliosis between rmTBI and control (naïve or SHAM) 3xTg-AD mouse groups. <b>Conclusions:</b> Collectively, our data show that rmTBIs early in life do not accelerate progression or enhance the magnitude of disease in mice that are genetically predisposed to developing AD. These findings suggest that the young brain is quite resilient to trauma and that an enhanced risk of neurodegeneration is not an inescapable conclusion of a history of rmTBI.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476274"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722021","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":"Risk factors and cognitive domain markers of progression in subjective cognitive decline.","authors":"Omonigho M Bubu, Alfred K Mbah, Mark A Bernard, Anthony Briggs, Arline Faustin, Lindsey Gurin, Julia A Rao, Sakina Ouedraogo Tall, Ricardo S Osorio, Arjun V Masurkar","doi":"10.1177/13872877261470393","DOIUrl":"10.1177/13872877261470393","url":null,"abstract":"<p><p>BackgroundSubjective cognitive decline (SCD) is increasingly recognized in some cases as an early clinical stage in the Alzheimer's disease continuum, yet the factors that predict which individuals will progress to objective impairment remain poorly understood.ObjectiveWe evaluated risk factor differences and cognitive domain markers associated with progression in participants with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer's Disease Research Center.MethodsWe included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, <i>APOE</i> status, psychometric test performance and comorbidities with longitudinal-decline.ResultsOverall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) versus 17.3 (2.1)), Hispanic ethnicity (50.0% versus 11.0%), and hypercholesterolemia (adjusted odds ratio: 6.67) were risk factors for progression in SCD, <i>p</i> ≤ 0.05, whereas <i>APOE</i> status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (<i>p</i> < 0.001 for all).ConclusionsThese findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261470393"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of cerebrospinal fluid tau biomarkers in amyloid-negative A-T + N + neurodegeneration: A retrospective cohort study.","authors":"Aslı Aksoy Gündoğdu, Bedia Samancı, Merve Alaylıoğlu, Erdi Şahin, Çağrı Ulukan, İbrahim Hakan Gürvit, Erdinç Dursun, Haşmet Ayhan Hanağası, Duygu Gezen-Ak, Başar Bilgiç","doi":"10.1177/13872877261476236","DOIUrl":"10.1177/13872877261476236","url":null,"abstract":"<p><p>BackgroundAmyloid-negative tau-related neurodegeneration represents a non-Alzheimer biomarker-defined profile; however, its clinical heterogeneity and prognostic relevance remain unclear within Alzheimer's disease-related frameworks.ObjectiveTo characterize the clinical spectrum and identify predictors of mortality in patients with this profile.MethodsIn this retrospective cohort study, 1280 patients evaluated at a tertiary neurology center were screened, and 130 with an amyloid-negative cerebrospinal fluid (CSF) pattern [amyloid-β (Aβ)₄₂ normal, phosphorylated tau (pTau), and total tau (tTau) elevated] were included. Survival was assessed using Kaplan-Meier analysis, and predictors of mortality were evaluated using Cox models.ResultsThe cohort (mean age 68.8 ± 10.1 years; 45.4% female) showed heterogeneous diagnoses, mainly mild cognitive impairment and frontotemporal dementia (each 30%). Survival differed across diagnostic groups (log-rank p = 0.037), with more favorable outcomes in mild cognitive impairment. Male sex was more frequent among non-survivors (88.9% versus 45.6%, p < 0.001). Higher CSF tTau levels were associated with mortality in the joint Cox model (HR 1.003, 95% CI 1.001-1.006, p = 0.006) and faster clinical progression (r = 0.22, p = 0.011). When modeled separately, neither tTau nor pTau was independently associated with mortality; however, both became significant in opposite directions when included jointly.ConclusionsThe amyloid-negative A-T + N + profile represents a clinically heterogeneous subgroup with prognostic relevance. CSF tTau was associated with mortality and faster clinical progression, but the joint-model findings involving tTau and pTau should be interpreted cautiously as hypothesis-generating. Further studies are needed to clarify the prognostic value of tau-related biomarkers in this population.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476236"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724057","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":"Identification of B-cell senescence-related key genes and mechanisms in Alzheimer's disease through transcriptomic sequencing combined with Mendelian randomization analysis and experimental verification.","authors":"Rong Yuan, Guihua Liao, Shaohui Su, Jiayan Shan, Shanhong Tang","doi":"10.1177/13872877261477008","DOIUrl":"10.1177/13872877261477008","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia. Currently, no treatment method can treat AD completely successfully.ObjectiveThis work seeks to uncover new genetic signatures linking B-cell senescence to AD, elucidate the immune-related pathological mechanisms of AD.MethodsThe GSE85426 and GSE168813 for AD were obtained from public databases. Differential analysis of expression matrix in GSE85426 was conducted to screen differentially expressed genes (DEGs), WGCNA was explored to obtain B cell and cell senescence related hub genes. Then the key genes for AD were screened by intersection, Mendelian randomization (MR), receiver operating characteristic (ROC) curve, and Wilcoxon test. Additionally, enrichment analysis, immune infiltration analysis, and molecular docking were performed to investigate the molecular mechanism of key genes and drug targets related to key genes, respectively.ResultsIn this study, CCDC86 and PARP9 were identified as key genes, genetic association analysis suggested CCDC86 correlates with higher AD susceptibility while PARP9 tends to correlate with lowered AD risk. We also found that these two key genes were highly correlated with B cells, and the abundance of B cells in AD increased significantly. Finally, our calculation revealed that the binding free energy between PARP9 and bisphenol A was -7.6 kcal/mol, implying a favorable simulated binding tendency between the two molecules.ConclusionsThese findings suggest that PARP9 may serve as a promising and reliable drug target for clinical therapy, which may represent a tentative candidate worthy of further experimental validation for subsequent biomarker and therapeutic target research in AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261477008"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722213","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":"Effects of damaged astrocytes on DNA damage and repair in human neurons: Implications for Alzheimer's disease.","authors":"Starr Welty, Michael Bagnell, Fulin Ma, Karl Herrup, Arthur Samuel Levine","doi":"10.1177/13872877261476036","DOIUrl":"https://doi.org/10.1177/13872877261476036","url":null,"abstract":"<p><p>BackgroundStudies suggest a strong association between astrocytes, neuronal DNA damage, elevated amyloid-β, and brain degeneration in Alzheimer's disease (AD).ObjectiveThis study aimed to show whether astrocytes with damaged DNA affect human neuronal progenitor cells (NPCs) or differentiated neurons in close proximity, dependent on astrocytic <i>APOE</i> allele expression.MethodsImmortalized human astrocytes (hTERT) expressing <i>APOE</i> were treated with etoposide to induce DNA damage and co-cultured in a transwell system with human NPCs or differentiated neurons. We used western blotting and immunostaining to evaluate the DNA damage response of the NPCs and neurons.ResultsUndamaged NPCs showed increased DNA damage when co-cultured with damaged astrocytes. The astrocytic <i>APOE</i> genotype had little to no effect on the transcellular damage response. NPCs overexpressing the amyloid-β protein precursor responded more robustly when co-cultured with damaged astrocytes. Differentiated neurons showed no significant changes in their DNA damage response to damaged astrocytes.ConclusionsThis study is the first to demonstrate that astrocytic DNA damage may contribute to early stages of neuronal pathology in AD by inducing a DNA damage response in vulnerable neuronal populations.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476036"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706631","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":"Individual alpha peak frequency tracks Alzheimer's disease progression: A longitudinal pilot study.","authors":"Ruimin Wang, Takao Yamasaki, Takako Mitsudo, Yoshitaka Matsuda, Satoru Goto, Takenao Sugi","doi":"10.1177/13872877261476331","DOIUrl":"https://doi.org/10.1177/13872877261476331","url":null,"abstract":"<p><p>BackgroundEarly and accurate tracking of Alzheimer's disease (AD) progression is critical for timely intervention. However, electrophysiological biomarkers capable of capturing long-term neurodegenerative changes remain largely underexplored.ObjectiveWe investigated whether individual alpha peak frequency (IAPF), an electroencephalography (EEG)-derived measure of dominant neural oscillatory activity, could serve as a longitudinal biomarker of AD progression.MethodsTwenty-seven patients with AD aged 63-91 years underwent annual EEG and cognitive assessments over 2-7 years. IAPF was extracted from eyes-closed resting-state EEG. Longitudinal associations among IAPF, Mini-Mental State Examination (MMSE) scores, age, and follow-up time were evaluated using repeated-measures correlation and linear mixed-effects models. Annual IAPF changes were compared with those of healthy controls (HC) aged 20-70 years, stratified by decade-based age subgroups. Longitudinal changes in relative spectral power were also analyzed.ResultsPatients with AD showed significant longitudinal declines in both IAPF and MMSE scores, with a positive longitudinal association between the two measures. Mixed-effects models indicated that these declines were better explained by follow-up time after accounting for baseline age than by age at assessment alone. Compared with all healthy-control age subgroups, patients with AD exhibited a significantly steeper annual IAPF decline. Relative theta power increased and alpha/beta power decreased over follow-up, consistent with spectral slowing. However, annualized spectral-power changes showed limited disease specificity, with significant AD-HC differences only for delta and alpha power relative to the oldest HC subgroup.ConclusionsThese findings support IAPF as a non-invasive, temporally sensitive, and clinically accessible biomarker for monitoring AD progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261476331"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706675","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":"Subthreshold early white-matter hyperintensity increase predicts accelerated hippocampal and whole-brain atrophy in anti-amyloid-β immunotherapy.","authors":"Shiori Amemiya, Hidemasa Takao, Shoya Matsumoto, Yumi Umeda-Kameyama, Yoshiki Niimi, Toshiyuki Kakumoto, Wataru Satake, Jun Mitsui, Sumito Ogawa, Osamu Abe","doi":"10.1177/13872877261475336","DOIUrl":"https://doi.org/10.1177/13872877261475336","url":null,"abstract":"<p><p>BackgroundAnti-amyloid-β (anti-Aβ) therapy slows cognitive decline but paradoxically accelerates whole-brain gray matter atrophy, complicating outcome prediction.ObjectiveTo identify early imaging markers that predict long-term prognoses.MethodsThis longitudinal cohort study prospectively enrolled participants with early Alzheimer's disease, initiating anti-Aβ therapy. We performed automated T1-weighted MRI volumetric analysis of the whole-brain gray matter, hippocampus, and white matter hyperintensities (WMH). Temporal dynamics were characterized using piecewise linear regression, and predictive utility was assessed using multivariate linear regression analyses.ResultsTwenty-two participants (74 ± 11 years; 14 women) were followed for 376 ± 146 days. Significant volume changes occurred in all regions (p < 0.01). No overt amyloid-related edema was detected, and hemorrhagic events were mild to moderate. Piecewise regression revealed an initial WMH surge that decelerated after 60 days (β=-0.19 [95%CI: -0.33, -0.042], p = 0.01), whereas gray matter regions showed linear volume decline. Early subthreshold WMH expansion predicted long-term atrophy independent of baseline covariates (age, sex, amyloid burden, mini-mental state examination score, drug, and hemorrhagic events) in the hippocampus (β=-0.058 [95%CI: -0.092, -0.025], p = 0.003), and whole-brain gray matter (β=-0.033 [95%CI: -0.065, -0.002], p = 0.04). Early whole-brain gray matter atrophy correlated with the WMH surge (β=-0.53 [95%CI: -0.69, -0.38], p < 0.001) and predicted long-term hippocampal atrophy (β=0.098 [95%CI: 0.038, 0.16], p = 0.004).ConclusionsA transient WMH surge within the first 60 days of therapy mirrors the known time course of amyloid-related imaging abnormalities. Along with concurrent early whole-brain volume loss, this surge independently predicts accelerated long-term hippocampal and whole-brain atrophy, highlighting its potential as an early prognostic imaging marker.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261475336"},"PeriodicalIF":3.4,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697559","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":"A working feedback-based framework for goal-directed spatial memory deficits in Alzheimer's disease: Feedforward and feedback interactions along the RSC-MEC-CA1-RSC axis.","authors":"Yaoyao Tian, Hong Qing, Zhenzhen Quan","doi":"10.1177/13872877261473933","DOIUrl":"https://doi.org/10.1177/13872877261473933","url":null,"abstract":"<p><p>Spatial navigation deficits are among the earliest and most clinically significant cognitive impairments in Alzheimer's disease (AD), particularly when navigation depends on goal-directed spatial memory. This review defines goal-directed spatial memory as a task-oriented construct and proposes a network-level framework for interpreting early AD navigation deficits. We synthesize anatomical, physiological, behavioral, and disease-related evidence concerning the retrosplenial cortex (RSC), medial entorhinal cortex (MEC), hippocampal CA1, and CA1-RSC feedback interactions. We propose the RSC-MEC-CA1-RSC axis as a testable working framework based on coordinated feedforward and feedback interactions. Within this system, the RSC integrates behaviorally relevant external cues and supports reference-frame transformation. The MEC contributes to path integration and self-goal relational coding, and CA1 consolidates these signals into functional goal-location representations. These representations can be retrieved, stabilized, and then transmitted back to cortical networks to guide continuous behavioral updating. Notably, we define the CA1-RSC pathway as a functional feedback route that supports iterative information updating, route correction and strategic adjustment. We argue that AD navigation deficits stem from the progressive breakdown of feedforward and feedback interactions across this axis, rather than from isolated dysfunction of single brain regions. The RSC-MEC-CA1-RSC framework offers a circuit-level mechanistic account for spatial disorientation in early AD. As a working model instead of a fully validated canonical circuit, it puts forward a series of testable hypotheses for future research, including cross-regional electrophysiological recordings, projection-specific circuit manipulation, imaging assessments, and differentiated navigation paradigms to examine cue use, path integration, goal retrieval and feedback-dependent updating.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261473933"},"PeriodicalIF":3.4,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697608","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":"Concordance between plasma biomarkers of phosphorylated tau and tau-PET: A narrative review.","authors":"Anna S Van Houwelingen, Meike W Vernooij, Marie R Vermeiren, Rik Ossenkoppele, Elsmarieke Van De Giessen, Harro Seelaar, Julia Neitzel","doi":"10.1177/13872877261468708","DOIUrl":"https://doi.org/10.1177/13872877261468708","url":null,"abstract":"<p><p>Plasma phosphorylated tau (p-tau) and tau positron emission tomography (PET) are key biomarkers for detecting tau pathology in Alzheimer's disease (AD), offering both diagnostic and prognostic value. However, the concordance between plasma p-tau (p-tau217/p-tau181/p-tau231) positivity and tau-PET positivity remains incompletely understood. In this narrative review, we show that concordance varies by clinical disease stage, the plasma p-tau biomarker assessed, the definition of tau-PET positivity, and the presence of comorbidities and other risk factors. We also present evidence for a temporal sequence of plasma p-tau changes, with plasma p-tau231 positivity preceding p-tau181 positivity, followed by plasma p-tau217 reflecting more advanced stages of tau pathology. We highlight the relevance of these temporal dynamics for the potential development of a stage-specific trajectory framework for plasma p-tau and discuss how such a framework may support improved integration of plasma p-tau and tau-PET, thereby enhancing screening efficiency. Finally, we outline methodological challenges, highlight current efforts such as the development of tau-PET harmonization strategies, and identify priorities for future research. Taken together, this review provides a comprehensive overview of the factors influencing concordance between plasma p-tau positivity and tau-PET positivity. Careful consideration of these factors will be essential for the optimal integration of these biomarkers across the AD spectrum, with the potential to improve both diagnostic and therapeutic strategies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261468708"},"PeriodicalIF":3.4,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697627","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}