Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

{"title":"Imaging for anti-amyloid therapy eligibility: Comparing GRE and SWI in detecting microhemorrhages and superficial siderosis.","authors":"Jeremy N Ford, Suely Fazio Ferraciolli, Odette Ganem Chagui, Marvin Relerford, Esteban Calle Cadavid, John Dickson, Maryam Vejdani-Jahromi, Matthew N DeSalvo, Liliana A Ramirez Gomez, Seonghwan Yee, Harry R Griffin, Benjamin Kozak, Saurabh Rohatgi, Raymond Y Huang, Teresa Gomez-Isla, Javier Romero","doi":"10.1002/dad2.70477","DOIUrl":"10.1002/dad2.70477","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-amyloid therapies such as lecanemab require magnetic resonance imaging (MRI) screening to exclude patients with > 4 gradient-recalled echo (GRE)-detected microhemorrhages or any superficial siderosis (SS). Although GRE and susceptibility-weighted imaging (SWI) are both accepted, they differ in detection performance.</p><p><strong>Methods: </strong>We retrospectively analyzed 224 eligibility MRIs with paired GRE and SWI from a single academic health system. Six neuroradiologists assessed a 20-scan reliability subset; the remaining 204 scans were assigned to one rater for hemorrhagic lesion detection and MRI-based eligibility classification. Interobserver reliability was calculated using intraclass correlation coefficients (ICCs), and sequence differences were evaluated using non-parametric tests.</p><p><strong>Results: </strong>SWI detected more microhemorrhages than GRE (mean 1.24 vs. 0.67, <i>p <</i> 0.0001), identified eight additional SS cases, and showed higher interobserver agreement (ICC 0.951 vs. 0.764, <i>p <</i> 0.01). SWI classified more patients as MRI ineligible than GRE (26/204 [12.7%] vs. 11/204 [5.4%]).</p><p><strong>Discussion: </strong>SWI identifies more exclusionary hemorrhagic findings and demonstrates greater reproducibility than GRE.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70477"},"PeriodicalIF":4.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P-tau181 is longitudinally associated with a proxy measure of mild behavioral impairment among frail older adults: Insights from COGFRAIL.","authors":"Federico Bellelli, Emmanuel González, Alberta Peluso, Davide Angioni, Sandrine Sourdet, Maria Soto Martin","doi":"10.1002/dad2.70392","DOIUrl":"10.1002/dad2.70392","url":null,"abstract":"<p><strong>Introduction: </strong>Cross-sectional studies link Alzheimer's disease (AD) pathogenesis to mild behavioral impairment (MBI), but longitudinal evidence remains limited. We examined whether plasma phosphorylated tau (p-tau)181 predicts progression of an MBI-proxy over 2 years in pre-frail and frail older adults with mild cognitive impairment.</p><p><strong>Methods: </strong>This is a secondary analysis of the Cognitive Function and Prevalence of Amyloid Marker in Frail Older Adults study, including 174 participants (mean age = 82.9 ± 5.4 years). Plasma p-tau181 was analyzed both as a continuous variable and by tertiles. MBI was approximated using a Neuropsychiatric Inventory Questionnaire (NPI-Q)-based algorithm.</p><p><strong>Results: </strong>Participants in the highest tertile showed greater progression in the number of affected NPI-Q-derived MBI domains and overall severity compared to the lowest tertile. Continuous analyses showed a similar but non-significant trend (<i>P</i> = 0.08).</p><p><strong>Discussion: </strong>Amyloid and tau pathology may contribute not only to cognitive but also to behavioral impairment, supporting the hypothesis that MBI reflects underlying AD pathology, and may help identify individuals at higher risk of neuropsychiatric progression.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70392"},"PeriodicalIF":4.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking cognitive variability and Alzheimer's disease biomarkers by neurocognitive status.","authors":"Shayne S-H Lin, Alicia Milam, Andrew M Kiselica, Stephen L Aita, Mubarick Saeed, Troy Webber, Steven Paul Woods, Nicholas C Borgogna, Keenan A Walker, Vidyulata Kamath, Kristina Visscher, Charles F Murchison, David S Geldmacher, Erik D Roberson, Benjamin D Hill, Victor A Del Bene","doi":"10.1002/dad2.70481","DOIUrl":"10.1002/dad2.70481","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess intra-individual cognitive variability (IICV) in relation to Alzheimer's disease (AD) biomarkers.</p><p><strong>Methods: </strong>The National Alzheimer's Coordinating Center sample (<i>n</i> = 879), aged 50+ with a complete neuropsychological evaluation and AD biomarker data available (64% cognitively intact; 36% cognitively impaired). Moderated regression models using AD biomarkers, neurocognitive status, and interaction effects predicted IICV. AD biomarkers included cerebrospinal fluid (CSF) measures of Aβ_1-42, phosphorylated tau 181 (p-Tau₁₈₁), total tau (t-Tau), and amyloid positron emission tomography.</p><p><strong>Results: </strong>Increased AD biomarker burden was associated with increased IICV among cognitively impaired individuals (correlational strength ranging from 0.149 to 0.460) but not among the cognitively intact group.</p><p><strong>Discussion: </strong>Increases in measures of amyloid, soluble tau, and neurodegeneration are associated with increased IICV among cognitively impaired older adults. The findings underscore the potential of IICV as a sensitive outcome measure. Future studies should replicate findings longitudinally and in more diverse samples.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70481"},"PeriodicalIF":4.4,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AST/ALT, <i>APOE</i> ε4, and Alzheimer's disease progression: A longitudinal cohort study.","authors":"Young Hyeon Ahn, Chan-Mo Yang, Dae-Jin Kim, Sae Hwan Lee, Young Hyun Jung, Sang-Yeol Lee, Sung-Hoon Yoon","doi":"10.1002/dad2.70484","DOIUrl":"10.1002/dad2.70484","url":null,"abstract":"<p><strong>Introduction: </strong>The aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio is a routinely available liver-enzyme index. Whether apolipoprotein E (<i>APOE</i>) ε4 modifies associations of baseline AST/ALT with longitudinal Alzheimer's disease (AD) trajectories is unclear.</p><p><strong>Methods: </strong>In 2709 Alzheimer's Disease Neuroimaging Initiative participants, linear mixed-effects models estimated AST/ALT-associated longitudinal change in Mini-Mental State Examination, Alzheimer's Disease Assessment Scale 13-item Cognitive subscale, and AD-signature cortical thickness; Cox models evaluated continuous AST/ALT and an extreme-tertile <i>APOE</i> ε4 × AST/ALT comparison for clinical progression.</p><p><strong>Results: </strong>Higher baseline AST/ALT was associated with faster cognitive decline and AD-signature cortical thinning, with larger associations among <i>APOE</i> ε4 carriers (interaction <i>p</i> = .0006-0.040). In clinical-progression analyses, continuous AST/ALT was not significantly associated with risk (hazard ratio [HR] 1.07 per standard deviation, <i>p</i> = 0.12). In the extreme-tertile comparison, <i>APOE</i> ε4 carriers with high AST/ALT had the highest adjusted hazard (HR 3.08, 95% confidence interval 2.18-4.34), but multiplicative and additive interactions were null and incremental discrimination was minimal (Δ<i>C =</i> +0.003).</p><p><strong>Discussion: </strong>Baseline AST/ALT was associated with faster cognitive and cortical decline, particularly among <i>APOE</i> ε4 carriers, but provided limited incremental information for clinical progression beyond <i>APOE</i> ε4 and baseline diagnosis. These findings represent a large longitudinal extension of prior liver-enzyme observations and require external validation.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70484"},"PeriodicalIF":4.4,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elecsys pT181p immunoassay: Clinical performance for ruling out amyloid pathology.","authors":"Craig Ritchie, Sayuri Hortsch, Clara Quijano-Rubio, Patrick Menzel, Imke Kirste, David Caley, Anna D Burke, Christopher C Rowe, Marc Suárez-Calvet, Dag Aarsland, Jonathan Liss, Mercè Boada, David Watson, Mark Rapp","doi":"10.1002/dad2.70439","DOIUrl":"10.1002/dad2.70439","url":null,"abstract":"<p><strong>Introduction: </strong>Plasma biomarker rule-out tests can be used early in the Alzheimer's disease (AD) diagnostic pathway to identify people with low likelihood of amyloid pathology.</p><p><strong>Methods: </strong>A care setting-agnostic cutoff for the Elecsys^® Phospho-Tau (181P) plasma (pT181p) immunoassay was determined and validated in two independent, diverse cohorts, representative of real-world clinical practice (<i>N </i>= 604; <i>N</i> = 787, respectively). An additional cutoff was assessed in a subset of people reflective of primary care (<i>n </i>= 312).</p><p><strong>Results: </strong>At a care setting-agnostic cutoff of 0.934 pg/ml, high negative predictive value (NPV) (93.8%) and acceptable positive predictive value (PPV) (46.6%) were observed against amyloid-positron emission tomography (PET). A primary care-specific cutoff of 0.722 pg/ml showed high NPV (97.9%) against amyloid-PET. Amyloid positivity prevalence for each cutoff population was 22.5% and 13.1%, respectively.</p><p><strong>Discussion: </strong>The pT181p immunoassay is a high-performance test that may substantially help improve access to amyloid pathology testing for people requiring confirmation, potentially leading to timely clinical decisions and better outcomes.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70439"},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analyses of Alzheimer's disease blood biomarkers and cognitive domains.","authors":"Deirdre M O'Shea, James E Galvin","doi":"10.1002/dad2.70471","DOIUrl":"10.1002/dad2.70471","url":null,"abstract":"<p><strong>Introduction: </strong>Whether Alzheimer's disease (AD) blood biomarker-cognition associations differ across cognitive domains, analytic context, and biomarker modeling strategy in population-based cohorts is unclear.</p><p><strong>Methods: </strong>In 1170 older adults from the Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP), we examined cross-sectional (2016) and prospective (2016 to 2022) associations of blood phosphorylated tau at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and amyloid beta 42/40 ratio (Aβ42/40) with memory, executive function, language, visuospatial ability, and global cognition using individual-biomarker, principal component analysis-derived composite, and multi-biomarker panel models.</p><p><strong>Results: </strong>Cross-sectionally, NfL and GFAP showed the broadest associations with cognitive performance. In simultaneous models of baseline-adjusted follow-up cognition, p-tau181 was associated with lower memory (<i>β</i> = -0.080, <i>q</i> < 0.001) and global cognition (<i>β</i> = -0.066, <i>q</i> < 0.001), while GFAP was associated with lower executive function (<i>β</i> = -0.047, <i>q</i> = 0.007), memory (<i>β</i> = -0.047, <i>q</i> = 0.032), and global cognition (<i>β</i> = -0.066, <i>q</i> = 0.002). NfL and Aβ42/40 were not independently associated after mutual adjustment. P-tau181 also showed relative domain selectivity between memory and executive function. Relative model support differed by cognitive domain and analytic context.</p><p><strong>Discussion: </strong>AD blood-based biomarker-cognition associations were domain-differentiated and context-dependent: Concurrent associations did not reliably indicate associations with cognition 6 years later, and only p-tau181 showed formal evidence of relative memory-versus-executive selectivity. Exploratory pairwise comparisons highlighted p-tau181 + GFAP for follow-up memory and global cognition, warranting independent evaluation.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70471"},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma GFAP and language-network tau mediate the effect of amyloid burden on semantic fluency: A mediation analysis.","authors":"Wei Han, Na Li, Peishen Wang, Wenhao An, Xinye Han, Yihua An","doi":"10.1002/dad2.70475","DOIUrl":"10.1002/dad2.70475","url":null,"abstract":"<p><strong>Introduction: </strong>Amyloid burden may relate to semantic fluency through tau and astrocytic pathways, but their contributions remain unclear.</p><p><strong>Methods: </strong>In this cross-sectional study, we analyzed 210 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with amyloid positron emission tomography (PET), tau PET, plasma glial fibrillary acidic protein (GFAP), and animal fluency. Joint mediation models estimated indirect effects through language-network tau and GFAP, with subgroup analyses in amyloid beta (Aβ)-positive participants.</p><p><strong>Results: </strong>In the full sample, both tau and GFAP significantly mediated the association between amyloid burden and animal fluency, with a larger, more robust estimate for tau. Direct effects were non-significant. Among Aβ-positive participants, tau mediation remained significant, whereas GFAP mediation was attenuated. The dual-mediator model showed a significant combined indirect effect (average causal mediation effects [ACME] = -0.211). Exploratory analyses suggested possible apolipoprotein E <i>APOE</i> ε4 moderation of the tau-mediated pathway.</p><p><strong>Discussion: </strong>Amyloid-related semantic fluency impairment was associated with language-network tau and astrocytic reactivity, with tau the stronger mediator, supporting biomarker-defined heterogeneity in language vulnerability across the Alzheimer's continuum.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70475"},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive function and eye movement patterns during reading tasks in older adults.","authors":"Haiwei Zuo, King Hann Lim, Heming Huang, Sivaraman Eswaran, Jonathan Then Sien Phang, Luping Song, Chenhui Zhang, Zhenjun Li, Hongming Huang","doi":"10.1002/dad2.70464","DOIUrl":"10.1002/dad2.70464","url":null,"abstract":"<p><strong>Introduction: </strong>Progressive cognitive decline associated with aging can be measured by observing alterations in eye movement behavior during reading. This study explores the association between eye movement profiles and cognitive performance in older adults during reading-based tasks in virtual reality.</p><p><strong>Methods: </strong>Sixty older adults with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls (HC) wore a virtual reality (VR) headset during a reading-based task. Recorded eye movements yielded four gaze features (F₂-F₅): fixation duration, region of interest (ROI) entry count, regression count, and saccade amplitude. With the reading-task total score (F₁), these formed a five-feature set (F₁-F₅) for logistic regression under leakage-safe stratified 10-fold cross-validation. Concurrent validity was assessed against paper-based Mini-Mental State Examination (MMSE).</p><p><strong>Results: </strong>The reading-task total score was strongly correlated with MMSE (<i>r =</i> 0.92, <i>p <</i> 0.001). Eye-tracking features showed significant group differences, with longer fixation duration, more ROI entries, more reading-order regressions, and larger saccade amplitude in cognitively impaired groups. The three-class combined model reached macro area under the curve (AUC) = 1.000, accuracy = 0.997, and macro F1 = 0.997; for MCI versus HC, eye-tracking-only and combined models reached AUC = 1.000 compared with AUC = 0.895 for the reading-task score alone.</p><p><strong>Discussion: </strong>Integrating gaze features with the reading-task total score can improve cognitive assessment by capturing process-level information. Participants with AD and MCI exhibited longer fixation durations, more ROI entries, and more reading regressions than controls, with the largest effects in AD. The combined model showed its clearest value in the three-class setting.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70464"},"PeriodicalIF":4.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging language markers and pathology: correlations between digital speech measures and surrogate CSF biomarkers in Alzheimer's disease.","authors":"Yijiang Pang, Liu Chen, Hiroko H Dodge, Jiayu Zhou","doi":"10.1002/dad2.70466","DOIUrl":"10.1002/dad2.70466","url":null,"abstract":"<p><strong>Introduction: </strong>Digital language markers show promise in detecting early cognitive impairment related to Alzheimer's disease (AD), yet their relationship with cerebrospinal fluid (CSF) biomarkers of AD pathology remains unclear mainly due to the lack of data with both CSF and language markers.</p><p><strong>Methods: </strong>Using National Alzheimer's Coordinating Center (NACC) clinical data as anchor variables, language makers in the Internet-Based Conversational Engagement Randomized Controlled Clinical Trial (I-CONECT) study were linked to NACC CSF data. Surrogate CSF biomarkers were created for I-CONECT subjects using machine learning models from common NACC clinical variables. Correlations assessed associations between CSF and language markers.</p><p><strong>Results: </strong>Lower predicted CSF amyloid beta correlated significantly with reduced syntactic complexity and shorter speech responses. Higher predicted total tau and phosphorylated tau correlated with reduced syntactic complexity.</p><p><strong>Discussion: </strong>This study demonstrates novel links between language markers and fluid biomarkers, highlighting conversational language as a potential accessible, non-invasive approach for early detection and monitoring of Alzheimer's pathology.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70466"},"PeriodicalIF":4.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From amyloid PET to plasma biomarkers: A multimodal imaging framework for early diagnosis and staging of Alzheimer's disease.","authors":"Jiayu Liu, Chou Xu, Yuxin Wang, Junfeng Zhang, Rui Hui, Wenying Lv, Ao Xu, Yuanyuan Dang, Schichao Su, Hulin Zhao, Yan Gao, Jianning Zhang","doi":"10.1002/dad2.70463","DOIUrl":"10.1002/dad2.70463","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is biologically defined by amyloid beta and tau pathology. Available biomarkers enable early diagnosis but differ in targets, accessibility, and utility. This review synthesizes evidence for plasma biomarkers, magnetic resonance imaging (MRI), and positron emission tomography (PET) to develop a pragmatic, stage-aware framework for early diagnosis and staging.</p><p><strong>Methods: </strong>We conducted a narrative review of recent literature and professional guidance (2024-2026) covering plasma biomarkers; structural/functional MRI; and amyloid, tau, and fluorodeoxyglucose (FDG) PET. Evidence was organized by biological target, diagnostic role, disease stage, and intended-use population.</p><p><strong>Results: </strong>For symptomatic individuals, high-performance plasma biomarkers (especially phosphorylated tau at threonine 217 [p-tau217]) support scalable triage and biological enrichment. MRI provides anatomical, differential-diagnostic, and treatment-safety information. Amyloid PET offers biological confirmation; tau PET adds regional staging and prognosis; FDG PET characterizes synaptic dysfunction and distinguishes dementia patterns. Emerging endogenously cleaved microtubule-binding region tau containing residue 243 (eMTBR-tau243) and brain-derived p-tau217 remain investigational. In cognitively unimpaired at-risk individuals, routine screening is not implied; use is for research or trial enrichment.</p><p><strong>Discussion: </strong>The preferred pathway is sequential: clinical evaluation and MRI establish context, validated plasma tests guide referral, and PET resolves uncertainty or refines staging when results may change management. This resource-aware integration improves diagnostic specificity and treatment decisions. Prospective implementation studies are needed to validate thresholds and equitable performance across diverse settings.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70463"},"PeriodicalIF":4.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}