{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:20:34Z","timestamp":1793578834347,"version":"4.5.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Importance<\/jats:title>\n Blood-based biomarkers (BBMs) demonstrate high accuracy in detecting Alzheimer disease (AD) pathological changes in symptomatic individuals. In autosomal dominant AD and in individuals with Down syndrome, both populations with near-universal development of AD pathology, elevations in BBMs are detectable years before clinical onset, supporting their utility for identifying preclinical disease in these cases. Among BBMs, plasma phosphorylated tau 217 (p-tau217) exhibits strong concordance with established in vivo markers of AD pathology. However, its ability to identify older adults without cognitive impairment who are amyloid-positive remains variable across studies and settings.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the standardized effect size of mean differences and classification accuracy of p-tau217 for published studies that compared amyloid-positive and amyloid-negative older adults without cognitive impairment.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n PubMed, Embase, and EBSCOhost databases from inception to September 1, 2025.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Observational studies or randomized clinical trials with baseline data on individuals without cognitive impairment who were classified as either amyloid positive or amyloid negative and reported numeric data for p-tau217 levels.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guideline was used for this study. Two authors independently carried out literature searches to identify studies with older adults without cognitive impairment who were classified as either amyloid positive or amyloid negative where p-tau217 was quantified.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measure<\/jats:title>\n \n The standardized mean difference (Hedges\n g<\/jats:italic>\n ) was used to characterize differences in mean p-tau217 levels. A pooled area under the curve (AUC) value was used to summarize the diagnostic accuracy of p-tau217 in identifying amyloid-positive individuals. Between-study heterogeneity was investigated using subgroup and sensitivity analyses. Publication bias was assessed using Egger tests.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Data for 7834 participants (2533 amyloid positive, 5301 amyloid negative) from 18 publications were analyzed. A large effect size was observed for p-tau217 (Hedges\n g<\/jats:italic>\n \u2009=\u20091.50; 95% CI, 1.33-1.68). Values for p-tau217 also demonstrated high accuracy for identifying amyloid-positive individuals without cognitive impairment (AUC\u2009=\u20090.87; 95% CI, 0.85-0.90).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n These findings demonstrate that plasma p-tau217 can reliably detect AD pathology in the preclinical stage. These findings support the clinical utility of plasma p-tau217 as a scalable, minimally invasive tool for early identification of AD, particularly in settings where timely intervention with disease-modifying therapies may offer the greatest benefit in slowing or preventing disease progression.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.4721","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T16:00:23Z","timestamp":1764604823000},"page":"13","source":"Crossref","is-referenced-by-count":26,"title":["Plasma Phosphorylated Tau 217 and Amyloid Burden in Older Adults Without Cognitive Impairment"],"prefix":"10.1001","volume":"83","author":[{"given":"Michael","family":"Malek-Ahmadi","sequence":"first","affiliation":[{"name":"Banner Alzheimer\u2019s Institute, Phoenix, Arizona"},{"name":"University of Arizona College of Medicine\u2013Phoenix, Phoenix"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Mountain Ridge High School, Glendale, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawaz","family":"Stipho","sequence":"additional","affiliation":[{"name":"University of Arizona College of Medicine\u2013Tucson, Tucson"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Denkinger","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpana","family":"Singh","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute, Sun City, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagner S.","family":"Brum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"},{"name":"Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Banner Alzheimer\u2019s Institute, Phoenix, Arizona"},{"name":"Banner Sun Health Research Institute, Sun City, Arizona"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"noi250082r1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease.","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement"},{"issue":"8","key":"noi250082r2","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup.","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"8","key":"noi250082r3","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.3390\/cells12081184","article-title":"Utility of blood-based tau biomarkers for mild cognitive impairment and Alzheimer\u2019s disease: systematic review and meta-analysis.","volume":"12","author":"Zabala-Findlay","year":"2023","journal-title":"Cells"},{"issue":"7","key":"noi250082r4","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1093\/brain\/awaf033","article-title":"Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer\u2019s disease spectrum.","volume":"148","author":"Fern\u00e1ndez Arias","year":"2025","journal-title":"Brain"},{"issue":"2","key":"noi250082r5","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/brain\/awae346","article-title":"A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests.","volume":"148","author":"Warmenhoven","year":"2025","journal-title":"Brain"},{"issue":"8","key":"noi250082r6","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jama.2020.12134","article-title":"Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders.","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA"},{"issue":"5","key":"noi250082r7","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/s43587-025-00835-z","article-title":"Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials.","volume":"5","author":"Ossenkoppele","year":"2025","journal-title":"Nat Aging"},{"issue":"6","key":"noi250082r8","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1038\/s41591-025-03622-w","article-title":"Plasma phospho-tau217 for Alzheimer\u2019s disease diagnosis in primary and secondary care using a fully automated platform.","volume":"31","author":"Palmqvist","year":"2025","journal-title":"Nat Med"},{"issue":"11","key":"noi250082r9","doi-asserted-by":"crossref","first-page":"8074","DOI":"10.1002\/alz.14315","article-title":"Head-to-head comparison of leading blood tests for Alzheimer\u2019s disease pathology.","volume":"20","author":"Schindler","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"15","key":"noi250082r10","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1001\/jama.2024.13855","article-title":"Blood biomarkers to detect Alzheimer disease in primary care and secondary care.","volume":"332","author":"Palmqvist","year":"2024","journal-title":"JAMA"},{"issue":"12","key":"noi250082r11","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-011458","article-title":"Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS).","volume":"6","author":"Downes","year":"2016","journal-title":"BMJ Open"},{"issue":"6","key":"noi250082r12","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1177\/0962280216669183","article-title":"Optimally estimating the sample mean from the sample size, median, mid-range, and\/or mid-quartile range.","volume":"27","author":"Luo","year":"2018","journal-title":"Stat Methods Med Res"},{"key":"noi250082r13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1471-2288-14-135","article-title":"Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range.","volume":"14","author":"Wan","year":"2014","journal-title":"BMC Med Res Methodol"},{"issue":"19","key":"noi250082r15","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1002\/sim.942","article-title":"A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations.","volume":"20","author":"Rutter","year":"2001","journal-title":"Stat Med"},{"issue":"3","key":"noi250082r16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","article-title":"Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology.","volume":"81","author":"Ashton","year":"2024","journal-title":"JAMA Neurol"},{"issue":"8","key":"noi250082r17","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70469","article-title":"Comparison of plasma p-tau217\/A\u00df42, p-tau217, and A\u00df42\/A\u00df40 biomarkers by race to detect Alzheimer\u2019s disease.","volume":"21","author":"Cousins","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"1","key":"noi250082r18","article-title":"Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer\u2019s continuum.","volume":"14","author":"Dor\u00e9","year":"2022","journal-title":"Alzheimers Dement (Amst)"},{"issue":"10","key":"noi250082r19","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1002\/alz.13393","article-title":"Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals.","volume":"19","author":"Ferreira","year":"2023","journal-title":"Alzheimers Dement"},{"key":"noi250082r20","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2025.105741","article-title":"A plasma biomarker panel for detecting early amyloid-\u00df accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer\u2019s disease.","volume":"116","author":"Gonz\u00e1lez-Escalante","year":"2025","journal-title":"EBioMedicine"},{"issue":"2","key":"noi250082r21","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1002\/alz.13525","article-title":"A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer\u2019s disease.","volume":"20","author":"Gonzalez-Ortiz","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"1","key":"noi250082r22","doi-asserted-by":"crossref","DOI":"10.1002\/alz.14297","article-title":"The Taiwan-ADNI workflow toward integrating plasma p-tau217 into prediction models for the risk of Alzheimer\u2019s disease and tau burden.","volume":"21","author":"Huang","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"2","key":"noi250082r23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/alz.12395","article-title":"Detecting amyloid positivity in early Alzheimer\u2019s disease using combinations of plasma A\u00df42\/A\u00df40 and p-tau.","volume":"18","author":"Janelidze","year":"2022","journal-title":"Alzheimers Dement"},{"issue":"1","key":"noi250082r24","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13195-025-01826-3","article-title":"Plasma phosphorylated tau 217 and amyloid-\u00df 42\/40 for amyloid risk in subgroups.","volume":"17","author":"Kang","year":"2025","journal-title":"Alzheimers Res Ther"},{"issue":"4","key":"noi250082r25","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1001\/jamaneurol.2022.5272","article-title":"Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers.","volume":"80","author":"Mattsson-Carlgren","year":"2023","journal-title":"JAMA Neurol"},{"issue":"5","key":"noi250082r26","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1002\/alz.13764","article-title":"Clinical validation of the PrecivityAD2 blood test: a mass spectrometry-based test with algorithm combining %p-tau217 and A\u00df42\/40 ratio to identify presence of brain amyloid.","volume":"20","author":"Meyer","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"7","key":"noi250082r27","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/s41591-022-01822-2","article-title":"Performance of plasma phosphorylated tau 181 and 217 in the community.","volume":"28","author":"Mielke","year":"2022","journal-title":"Nat Med"},{"issue":"4","key":"noi250082r28","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1002\/alz.13722","article-title":"The Bio-Hermes study: biomarker database developed to investigate blood-based and digital biomarkers in community-based, diverse populations clinically screened for Alzheimer\u2019s disease.","volume":"20","author":"Mohs","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"1","key":"noi250082r29","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13195-024-01469-w","article-title":"Combining plasma A\u00df and p-tau217 improves detection of brain amyloid in non-demented elderly.","volume":"16","author":"Niimi","year":"2024","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"noi250082r30","doi-asserted-by":"crossref","DOI":"10.1002\/alz.14430","article-title":"Influence of medical conditions on the diagnostic accuracy of plasma p-tau217 and p-tau217\/A\u00df42.","volume":"21","author":"Olvera-Rojas","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"4","key":"noi250082r31","doi-asserted-by":"crossref","first-page":"823","DOI":"10.14283\/jpad.2024.134","article-title":"Longitudinal phospho-tau217 predicts amyloid positron emission tomography in asymptomatic Alzheimer\u2019s disease.","volume":"11","author":"Rissman","year":"2024","journal-title":"J Prev Alzheimers Dis"},{"issue":"2","key":"noi250082r32","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/alz.13542","article-title":"Plasma A\u00df42\/A\u00df40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer\u2019s disease.","volume":"20","author":"Rissman","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"4","key":"noi250082r33","article-title":"Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort: the Shanghai Aging Study.","volume":"15","author":"Xiao","year":"2023","journal-title":"Alzheimers Dement (Amst)"},{"issue":"5","key":"noi250082r34","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70288","article-title":"The performance of plasma p-tau217 in Black middle-aged and older adults.","volume":"21","author":"Ennis","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"7","key":"noi250082r35","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41582-024-00977-5","article-title":"Acceptable performance of blood biomarker tests of amyloid pathology: recommendations from the Global CEO Initiative on Alzheimer\u2019s Disease.","volume":"20","author":"Schindler","year":"2024","journal-title":"Nat Rev Neurol"},{"key":"noi250082r40","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105545","article-title":"A blood test for Alzheimer\u2019s disease: a decade of progress and success.","volume":"112","author":"Ashton","year":"2025","journal-title":"EBioMedicine"},{"issue":"12","key":"noi250082r41","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/s41591-022-02074-w","article-title":"Differential roles of A\u00df42\/40, p-tau231 and p-tau217 for Alzheimer\u2019s trial selection and disease monitoring.","volume":"28","author":"Ashton","year":"2022","journal-title":"Nat Med"},{"issue":"2","key":"noi250082r42","doi-asserted-by":"crossref","DOI":"10.1002\/alz.14508","article-title":"The Alzheimer\u2019s Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau round robin study.","volume":"21","author":"Ashton","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"4","key":"noi250082r43","doi-asserted-by":"crossref","DOI":"10.1002\/alz.70208","article-title":"A comparison of p-tau assays for the specificity to detect tau changes in Alzheimer\u2019s disease.","volume":"21","author":"Janelidze","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"12","key":"noi250082r44","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1002\/alz.12756","article-title":"The Alzheimer\u2019s Association appropriate use recommendations for blood biomarkers in Alzheimer\u2019s disease.","volume":"18","author":"Hansson","year":"2022","journal-title":"Alzheimers Dement"},{"key":"noi250082r14","unstructured":"Higgins? JPT, Li? T, Deeks? JJ, eds. Chapter 6: Choosing effect measures and computing estimates of effect. In: Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023. Accessed November 3, 2025. https:\/\/training.cochrane.org\/handbook\/current"},{"key":"noi250082r36","unstructured":"ClinicalTrials.gov. A study of remternetug (LY3372993) in early Alzheimer\u2019s disease (TRAILRUNNER-ALZ 3). Accessed July 18, 2025. https:\/\/clinicaltrials.gov\/study\/NCT06653153"},{"key":"noi250082r37","unstructured":"ClinicalTrials.gov. A study of JNJ-64042056 in participants with preclinical Alzheimer\u2019s disease (Retain). Accessed July 18, 2025. https:\/\/clinicaltrials.gov\/study\/NCT06544616"},{"key":"noi250082r38","unstructured":"ClinicalTrials.gov. A donanemab (LY3002813) study in participants with preclinical Alzheimer\u2019s disease (TRAILBLAZER-ALZ 3). Accessed July 18, 2025. https:\/\/clinicaltrials.gov\/study\/NCT05026866"},{"key":"noi250082r39","unstructured":"Federal Register. Medical devices; laboratory developed tests. Accessed December 3, 2024. https:\/\/www.federalregister.gov\/documents\/2024\/05\/06\/2024-08935\/medical-devices-laboratory-developed-tests#h-10"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2842195\/jamaneurology_malekahmadi_2025_oi_250082_1767644873.17036.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T16:01:21Z","timestamp":1768233681000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2842195"}},"subtitle":["A Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2025.4721","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}