{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:52:55Z","timestamp":1777949575680,"version":"3.51.4"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":123,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is the leading cause of dementia worldwide and is pathologically defined by amyloid-\u03b2 and tau accumulation. Current diagnostic methods, such as PET imaging and cerebrospinal fluid (CSF) assays, are accurate but invasive, costly, and limited in accessibility. Plasma phosphorylated tau at threonine 217 (p-tau217) has emerged as a promising blood-based biomarker, but evidence from individual studies remains heterogeneous. We conducted a systematic review and meta-analysis to evaluate the diagnostic performance of plasma p-tau217 for AD. Following PRISMA guidelines, PubMed, Scopus, and Web of Science were searched up to July 2025. Eligible studies included clinical or biomarker-defined AD cohorts that reported plasma p-tau217 accuracy against amyloid or tau positivity or clinical diagnosis. Data on sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were extracted. Study quality was assessed using QUADAS-2. Pooled estimates were calculated using a Bayesian bivariate model, and heterogeneity was explored with meta-regression and subgroup analyses. Twenty-seven studies including 19,652 participants were analyzed. Plasma p-tau217 demonstrated high diagnostic accuracy for biomarker-defined AD, with pooled sensitivity of 85.4% (95% posterior intervals [PI]: 81.4\u201388.7), specificity of 88.0% (95% PI: 85.1\u201390.6), positive likelihood ratio (PLR) 7.13, negative likelihood ratio (NLR) 0.167, and DOR 42.7. Performance was consistent across amyloid PET and CSF reference standards. Subgroup analyses showed robust accuracy for amyloid positivity (sensitivity 87.3%, specificity 85.5%), tau positivity (sensitivity 84.9%, specificity 93.8%), and clinical AD diagnosis (sensitivity 72.9%, specificity 89.5%). Plasma p-tau217 consistently outperformed other blood biomarkers and correlated with cognitive decline, frailty, and behavioral impairment. Risk of bias was generally low, with no major publication bias detected. This meta-analysis indicates that plasma p-tau217 demonstrates promising diagnostic accuracy for detecting AD pathology across biomarker-defined reference standards. However, heterogeneity across assays, populations, and reference definitions, along with the use of optimized cut-offs in some studies and the limited power of publication-bias assessments, warrant cautious interpretation. Plasma p-tau217 appears well suited as a triage biomarker to guide confirmatory testing, but further large, prospectively designed studies with standardized assays and externally validated thresholds are needed before widespread clinical implementation.<\/jats:p>","DOI":"10.1007\/s12035-026-05864-2","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:26:41Z","timestamp":1777858001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Cerebrospinal Fluid to Blood Draw: Plasma p-Tau217 as a Non-Invasive Biomarker for Alzheimer\u2019s Disease: A Fagan Nomogram-Based Meta-Analytic Study"],"prefix":"10.1007","volume":"63","author":[{"given":"Nesma M.","family":"Gebril","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelrahman M.","family":"Elettreby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abeer H.","family":"Younis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa Hossam El Din","family":"Moawad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afaf M.","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gamal El","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kariman M.","family":"Abdelrahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah M.","family":"El-Kot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"5864_CR1","first-page":"30","volume":"2022","author":"S Gauthier","year":"2021","unstructured":"Gauthier S, Rosa-Neto P, Morais JA, Webster C (2021) World Alzheimer Report 2021: Journey through the diagnosis of dementia. Alzheimer\u2019s disease International 2022:30","journal-title":"Alzheimer\u2019s disease International"},{"key":"5864_CR2","doi-asserted-by":"publisher","unstructured":"\"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019\" (in eng). Lancet Public Health, 7(2):e105\u2013e125. https:\/\/doi.org\/10.1016\/s2468-2667(21)00249-8","DOI":"10.1016\/s2468-2667(21)00249-8"},{"issue":"10248","key":"5864_CR3","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/s0140-6736(20)30367-6","volume":"396","author":"G Livingston","year":"2020","unstructured":"Livingston G et al (2020) Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 396(10248):413\u2013446. https:\/\/doi.org\/10.1016\/s0140-6736(20)30367-6","journal-title":"Lancet"},{"issue":"6","key":"5864_CR4","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med 8(6):595\u2013608. https:\/\/doi.org\/10.15252\/emmm.201606210","journal-title":"EMBO Mol Med"},{"issue":"1","key":"5864_CR5","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17(1):5\u201321. https:\/\/doi.org\/10.1038\/nrn.2015.1","journal-title":"Nat Rev Neurosci"},{"issue":"12","key":"5864_CR6","doi-asserted-by":"publisher","first-page":"3286","DOI":"10.1093\/brain\/awx243","volume":"140","author":"A Bejanin","year":"2017","unstructured":"Bejanin A et al (2017) Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer\u2019s disease. Brain 140(12):3286\u20133300. https:\/\/doi.org\/10.1093\/brain\/awx243","journal-title":"Brain"},{"issue":"6","key":"5864_CR7","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1111\/joim.12816","volume":"284","author":"K Blennow","year":"2018","unstructured":"Blennow K, Zetterberg H (2018) Biomarkers for Alzheimer\u2019s disease: current status and prospects for the future. J Intern Med 284(6):643\u2013663. https:\/\/doi.org\/10.1111\/joim.12816","journal-title":"J Intern Med"},{"issue":"8","key":"5864_CR8","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.2967\/jnumed.111.089730","volume":"52","author":"VL Villemagne","year":"2011","unstructured":"Villemagne VL et al (2011) Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias. J Nucl Med 52(8):1210\u20131217. https:\/\/doi.org\/10.2967\/jnumed.111.089730","journal-title":"J Nucl Med"},{"issue":"4","key":"5864_CR9","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr.","year":"2018","unstructured":"Jack CR Jr. et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement 14(4):535\u2013562. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018","journal-title":"Alzheimers Dement"},{"issue":"9","key":"5864_CR10","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1001\/jamaneurol.2019.1632","volume":"76","author":"S Palmqvist","year":"2019","unstructured":"Palmqvist S et al (2019) Performance of fully automated plasma assays as screening tests for Alzheimer disease-related \u03b2-amyloid status. JAMA Neurol 76(9):1060\u20131069. https:\/\/doi.org\/10.1001\/jamaneurol.2019.1632","journal-title":"JAMA Neurol"},{"issue":"6","key":"5864_CR11","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","volume":"27","author":"O Hansson","year":"2021","unstructured":"Hansson O (2021) Biomarkers for neurodegenerative diseases. Nat Med 27(6):954\u2013963. https:\/\/doi.org\/10.1038\/s41591-021-01382-x","journal-title":"Nat Med"},{"issue":"7691","key":"5864_CR12","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nature25456","volume":"554","author":"A Nakamura","year":"2018","unstructured":"Nakamura A et al (2018) High performance plasma amyloid-\u03b2 biomarkers for Alzheimer\u2019s disease. Nature 554(7691):249\u2013254. https:\/\/doi.org\/10.1038\/nature25456. ((in eng))","journal-title":"Nature"},{"issue":"3","key":"5864_CR13","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41591-020-0755-1","volume":"26","author":"S Janelidze","year":"2020","unstructured":"Janelidze S et al (2020) Plasma P-tau181 in Alzheimer\u2019s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer\u2019s dementia. Nat Med 26(3):379\u2013386. https:\/\/doi.org\/10.1038\/s41591-020-0755-1. ((in eng))","journal-title":"Nat Med"},{"issue":"8","key":"5864_CR14","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1001\/jama.2020.12134","volume":"324","author":"S Palmqvist","year":"2020","unstructured":"Palmqvist S et al (2020) Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA 324(8):772\u2013781. https:\/\/doi.org\/10.1001\/jama.2020.12134. ((in eng))","journal-title":"JAMA"},{"issue":"7","key":"5864_CR15","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/s41582-022-00665-2","volume":"18","author":"TK Karikari","year":"2022","unstructured":"Karikari TK et al (2022) Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility. Nat Rev Neurol 18(7):400\u2013418. https:\/\/doi.org\/10.1038\/s41582-022-00665-2. ((in eng))","journal-title":"Nat Rev Neurol"},{"key":"5864_CR16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https:\/\/doi.org\/10.1136\/bmj.n71","journal-title":"BMJ"},{"issue":"8","key":"5864_CR17","doi-asserted-by":"publisher","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","volume":"155","author":"PF Whiting","year":"2011","unstructured":"Whiting PF et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529\u2013536. https:\/\/doi.org\/10.7326\/0003-4819-155-8-201110180-00009. ((in eng))","journal-title":"Ann Intern Med"},{"issue":"11","key":"5864_CR18","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/s0895-4356(03)00177-x","volume":"56","author":"AS Glas","year":"2003","unstructured":"Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM (2003) The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 56(11):1129\u20131135. https:\/\/doi.org\/10.1016\/s0895-4356(03)00177-x. ((in eng))","journal-title":"J Clin Epidemiol"},{"key":"5864_CR19","unstructured":"Macaskill P, Gatsonis C, Deeks  J, Harbord R, Takwoingi Y (eds) (2010) Cochrane handbook for systematic reviews of diagnostic test accuracy. Version. https:\/\/methods.cochrane.org\/sdt\/sites\/methods.cochrane.org.sdt\/files\/uploads\/Chapter%2010%20-%20Version%201.0.pdf"},{"issue":"9","key":"5864_CR20","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.jclinepi.2005.01.016","volume":"58","author":"JJ Deeks","year":"2005","unstructured":"Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58(9):882\u2013893. https:\/\/doi.org\/10.1016\/j.jclinepi.2005.01.016. ((in eng))","journal-title":"J Clin Epidemiol"},{"issue":"4","key":"5864_CR21","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1136\/eb-2013-101243","volume":"18","author":"CG Caraguel","year":"2013","unstructured":"Caraguel CG, Vanderstichel R (2013) The two-step Fagan\u2019s nomogram: ad hoc interpretation of a diagnostic test result without calculation. Evid Based Med 18(4):125\u2013128. https:\/\/doi.org\/10.1136\/eb-2013-101243. ((in eng))","journal-title":"Evid Based Med"},{"issue":"1","key":"5864_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s13690-021-00747-5","volume":"80","author":"VN Nyaga","year":"2022","unstructured":"Nyaga VN, Arbyn M (2022) Metadta: a Stata command for meta-analysis and meta-regression of diagnostic test accuracy data - a tutorial. Arch Public Health 80(1):95. https:\/\/doi.org\/10.1186\/s13690-021-00747-5","journal-title":"Arch Public Health"},{"key":"5864_CR23","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/978-1-4419-9019-8_23","volume":"537","author":"RC Boston","year":"2003","unstructured":"Boston RC, Sumner AE (2003) STATA: a statistical analysis system for examining biomedical data. Adv Exp Med Biol 537:353\u2013369. https:\/\/doi.org\/10.1007\/978-1-4419-9019-8_23. ((in eng))","journal-title":"Adv Exp Med Biol"},{"issue":"8","key":"5864_CR24","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1002\/alz.12301","volume":"17","author":"AM Brickman","year":"2021","unstructured":"Brickman AM et al (2021) Plasma p-tau181, p-tau217, and other blood-based Alzheimer\u2019s disease biomarkers in a multi-ethnic, community study. Alzheimers Dement 17(8):1353\u20131364. https:\/\/doi.org\/10.1002\/alz.12301. ((in eng))","journal-title":"Alzheimers Dement"},{"key":"5864_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146771","author":"F Dakterzada","year":"2025","unstructured":"Dakterzada F et al (2025) Performance of plasma phosphorylated tau-217 in patients on the continuum of Alzheimer\u2019s disease. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms26146771","journal-title":"Int J Mol Sci"},{"issue":"7","key":"5864_CR26","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1093\/brain\/awaf033","volume":"148","author":"J Fern\u00e1ndez Arias","year":"2025","unstructured":"Fern\u00e1ndez Arias J et al (2025) Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer\u2019s disease spectrum. Brain 148(7):2384\u20132399. https:\/\/doi.org\/10.1093\/brain\/awaf033","journal-title":"Brain"},{"issue":"3","key":"5864_CR27","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1001\/jamaneurol.2023.5319","volume":"81","author":"NJ Ashton","year":"2024","unstructured":"Ashton NJ et al (2024) Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol 81(3):255\u2013263. https:\/\/doi.org\/10.1001\/jamaneurol.2023.5319","journal-title":"JAMA Neurol"},{"issue":"5","key":"5864_CR28","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70288","volume":"21","author":"GE Ennis","year":"2025","unstructured":"Ennis GE et al (2025) The performance of plasma p-tau217 in Black middle-aged and older adults. Alzheimers Dement 21(5):e70288. https:\/\/doi.org\/10.1002\/alz.70288","journal-title":"Alzheimers Dement"},{"issue":"9","key":"5864_CR29","doi-asserted-by":"publisher","first-page":"6506","DOI":"10.1002\/alz.14140","volume":"20","author":"DJ Figdore","year":"2024","unstructured":"Figdore DJ et al (2024) Optimizing cutpoints for clinical interpretation of brain amyloid status using plasma p-tau217 immunoassays. Alzheimers Dement 20(9):6506\u20136516. https:\/\/doi.org\/10.1002\/alz.14140","journal-title":"Alzheimers Dement"},{"issue":"2","key":"5864_CR30","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70119","volume":"17","author":"M Ghahremani","year":"2025","unstructured":"Ghahremani M, Leon R, Smith EE, Ismail Z (2025) Exploring the association between mild behavioral impairment and plasma p-tau217: implications for early detection of Alzheimer\u2019s disease. Alzheimers Dement (Amst) 17(2):e70119. https:\/\/doi.org\/10.1002\/dad2.70119","journal-title":"Alzheimers Dement (Amst)"},{"issue":"2","key":"5864_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70116","volume":"17","author":"G Giacomucci","year":"2025","unstructured":"Giacomucci G et al (2025) The two cut-offs approach for plasma p-tau217 in detecting Alzheimer\u2019s disease in subjective cognitive decline and mild cognitive impairment. Alzheimers Dement (Amst) 17(2):e70116. https:\/\/doi.org\/10.1002\/dad2.70116","journal-title":"Alzheimers Dement (Amst)"},{"issue":"1","key":"5864_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13195-022-01005-8","volume":"14","author":"C Groot","year":"2022","unstructured":"Groot C et al (2022) Diagnostic and prognostic performance to detect Alzheimer\u2019s disease and clinical progression of a novel assay for plasma p-tau217. Alzheimers Res Ther 14(1):67. https:\/\/doi.org\/10.1186\/s13195-022-01005-8","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"5864_CR33","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad057","volume":"5","author":"EM Jonaitis","year":"2023","unstructured":"Jonaitis EM et al (2023) Plasma phosphorylated tau 217 in preclinical Alzheimer\u2019s disease. Brain Commun 5(2):fcad057. https:\/\/doi.org\/10.1093\/braincomms\/fcad057","journal-title":"Brain Commun"},{"issue":"1","key":"5864_CR34","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s13195-025-01826-3","volume":"17","author":"H Kang","year":"2025","unstructured":"Kang H et al (2025) Plasma phosphorylated tau 217 and amyloid\u2011\u03b2 42\/40 for amyloid risk in subgroups,. Alzheimers Res Ther 17(1):184. https:\/\/doi.org\/10.1186\/s13195-025-01826-3","journal-title":"Alzheimers Res Ther"},{"issue":"5","key":"5864_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2025.100092","volume":"12","author":"LM Li","year":"2025","unstructured":"Li LM et al (2025) Diagnostic and discriminative accuracy of plasma phosphorylated tau 217 for symptomatic Alzheimer\u2019s disease in a Chinese cohort. J Prev Alzheimers Dis 12(5):100092. https:\/\/doi.org\/10.1016\/j.tjpad.2025.100092","journal-title":"J Prev Alzheimers Dis"},{"issue":"7","key":"5864_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2025.100252","volume":"12","author":"H Moon","year":"2025","unstructured":"Moon H, Chen X (2025) Plasma p-tau217 predicting brain-wide tau accumulation in preclinical AD. J Prev Alzheimers Dis 12(7):100252. https:\/\/doi.org\/10.1016\/j.tjpad.2025.100252","journal-title":"J Prev Alzheimers Dis"},{"issue":"6","key":"5864_CR37","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1038\/s41591-025-03622-w","volume":"31","author":"S Palmqvist","year":"2025","unstructured":"Palmqvist S et al (2025) Plasma phospho-tau217 for Alzheimer\u2019s disease diagnosis in primary and secondary care using a fully automated platform. Nat Med 31(6):2036\u20132043. https:\/\/doi.org\/10.1038\/s41591-025-03622-w","journal-title":"Nat Med"},{"issue":"1","key":"5864_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01655-w","volume":"17","author":"N Pandey","year":"2025","unstructured":"Pandey N et al (2025) Plasma phospho-tau217 as a predictive biomarker for Alzheimer\u2019s disease in a large south American cohort,. Alzheimers Res Ther 17(1):1. https:\/\/doi.org\/10.1186\/s13195-024-01655-w","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"5864_CR39","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70078","volume":"17","author":"B Rajbanshi","year":"2025","unstructured":"Rajbanshi B et al (2025) Clinical and neuropathological associations of plasma A\u03b2(42)\/A\u03b2(40), p-tau217 and neurofilament light in sporadic frontotemporal dementia spectrum disorders,. Alzheimers Dement (Amst) 17(1):e70078. https:\/\/doi.org\/10.1002\/dad2.70078","journal-title":"Alzheimers Dement (Amst)"},{"issue":"4","key":"5864_CR40","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70003","volume":"16","author":"RZ Rousset","year":"2024","unstructured":"Rousset RZ et al (2024) Performance of plasma p-tau217 and NfL in an unselected memory clinic setting,. Alzheimers Dement (Amst) 16(4):e70003. https:\/\/doi.org\/10.1002\/dad2.70003","journal-title":"Alzheimers Dement (Amst)"},{"issue":"7","key":"5864_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70426","volume":"21","author":"MD Rudolph","year":"2025","unstructured":"Rudolph MD et al (2025) Evaluation of plasma p-tau217 for detecting amyloid pathology in a heterogeneous community-based cohort. Alzheimers Dement 21(7):e70426. https:\/\/doi.org\/10.1002\/alz.70426","journal-title":"Alzheimers Dement"},{"issue":"2","key":"5864_CR42","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.70107","volume":"17","author":"TT Saari","year":"2025","unstructured":"Saari TT et al (2025) Cross-sectional study of plasma phosphorylated tau 217 in persons without dementia,. Alzheimers Dement (Amst) 17(2):e70107. https:\/\/doi.org\/10.1002\/dad2.70107","journal-title":"Alzheimers Dement (Amst)"},{"issue":"2","key":"5864_CR43","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-12897-5","volume":"272","author":"J Sarto","year":"2025","unstructured":"Sarto J et al (2025) Accuracy and clinical applicability of plasma tau 181 and 217 for Alzheimer\u2019s disease diagnosis in a memory clinic cohort,. J Neurol 272(2):160. https:\/\/doi.org\/10.1007\/s00415-025-12897-5","journal-title":"J Neurol"},{"issue":"3","key":"5864_CR44","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14619","volume":"21","author":"KR Sewell","year":"2025","unstructured":"Sewell KR et al (2025) Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits. Alzheimers Dement 21(3):e14619. https:\/\/doi.org\/10.1002\/alz.14619","journal-title":"Alzheimers Dement"},{"issue":"9","key":"5864_CR45","doi-asserted-by":"publisher","first-page":"6456","DOI":"10.1002\/alz.14138","volume":"20","author":"P Thanapornsangsuth","year":"2024","unstructured":"Thanapornsangsuth P et al (2024) The Bayesian approach for real-world implementation of plasma p-tau217 in tertiary care memory clinics in Thailand. Alzheimers Dement 20(9):6456\u20136467. https:\/\/doi.org\/10.1002\/alz.14138","journal-title":"Alzheimers Dement"},{"issue":"9","key":"5864_CR46","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/s1474-4422(21)00214-3","volume":"20","author":"EH Thijssen","year":"2021","unstructured":"Thijssen EH et al (2021) Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer\u2019s disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study. Lancet Neurol 20(9):739\u2013752. https:\/\/doi.org\/10.1016\/s1474-4422(21)00214-3","journal-title":"Lancet Neurol"},{"issue":"5","key":"5864_CR47","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70303","volume":"21","author":"X Tian","year":"2025","unstructured":"Tian X et al (2025) Physical and biopsychosocial frailty, cognitive phenotypes, and plasma biomarkers for Alzheimer\u2019s disease in Chinese older adults: a population-based study. Alzheimers Dement 21(5):e70303. https:\/\/doi.org\/10.1002\/alz.70303","journal-title":"Alzheimers Dement"},{"issue":"7","key":"5864_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70465","volume":"21","author":"Q Wang","year":"2025","unstructured":"Wang Q et al (2025) Association and interaction of blood homocysteine and p-tau217 levels with temporal cortical thinning and cognitive impairment in Alzheimer\u2019s disease. Alzheimers Dement 21(7):e70465. https:\/\/doi.org\/10.1002\/alz.70465","journal-title":"Alzheimers Dement"},{"issue":"4","key":"5864_CR49","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12514","volume":"15","author":"Z Xiao","year":"2023","unstructured":"Xiao Z et al (2023) Plasma p-tau217, p-tau181, and NfL as early indicators of dementia risk in a community cohort: the Shanghai aging study,. Alzheimers Dement (Amst) 15(4):e12514. https:\/\/doi.org\/10.1002\/dad2.12514","journal-title":"Alzheimers Dement (Amst)"},{"issue":"2","key":"5864_CR50","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14536","volume":"21","author":"X Zhong","year":"2025","unstructured":"Zhong X et al (2025) Plasma p-tau217 and p-tau217\/A\u03b21-42 are effective biomarkers for identifying CSF- and PET imaging-diagnosed Alzheimer\u2019s disease: insights for research and clinical practice. Alzheimers Dement 21(2):e14536. https:\/\/doi.org\/10.1002\/alz.14536","journal-title":"Alzheimers Dement"},{"issue":"1","key":"5864_CR51","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/ene.13439","volume":"25","author":"CA Lane","year":"2018","unstructured":"Lane CA, Hardy J, Schott JM (2018) Alzheimer\u2019s disease. Eur J Neurol 25(1):59\u201370. https:\/\/doi.org\/10.1111\/ene.13439","journal-title":"Eur J Neurol"},{"key":"5864_CR52","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076518","author":"B Twarowski","year":"2023","unstructured":"Twarowski B, Herbet M (2023) Inflammatory processes in Alzheimer\u2019s disease-pathomechanism, diagnosis and treatment: a review,. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24076518","journal-title":"Int J Mol Sci"},{"issue":"1","key":"5864_CR53","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1021\/acschemneuro.9b00550","volume":"11","author":"X Xing","year":"2020","unstructured":"Xing X, Liu C, Ali A, Kang B, Li P, Ai H (2020) Novel disassembly mechanisms of sigmoid A\u03b2(42) protofibrils by introduced neutral and charged drug molecules. ACS Chem Neurosci 11(1):45\u201356. https:\/\/doi.org\/10.1021\/acschemneuro.9b00550","journal-title":"ACS Chem Neurosci"},{"key":"5864_CR54","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10030061","author":"C Villa","year":"2020","unstructured":"Villa C, Lavitrano M, Salvatore E, Combi R (2020) Molecular and imaging biomarkers in Alzheimer\u2019s disease: a focus on recent insights,. J Pers Med. https:\/\/doi.org\/10.3390\/jpm10030061","journal-title":"J Pers Med"},{"key":"5864_CR55","doi-asserted-by":"publisher","first-page":"100005","DOI":"10.1016\/j.bionps.2019.100005","volume":"1","author":"K Khoury","year":"2019","unstructured":"Khoury K, Ghossoub E (2019) Diagnostic biomarkers of Alzheimer\u2019s disease: A state-of-the-art review. Biomarkers in Neuropsychiatry 1:100005. https:\/\/doi.org\/10.1016\/j.bionps.2019.100005","journal-title":"Biomarkers in Neuropsychiatry"},{"issue":"3","key":"5864_CR56","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s13760-017-0816-5","volume":"117","author":"E Niemantsverdriet","year":"2017","unstructured":"Niemantsverdriet E, Valckx S, Bjerke M, Engelborghs S (2017) Alzheimer\u2019s disease CSF biomarkers: clinical indications and rational use. Acta Neurol Belg 117(3):591\u2013602. https:\/\/doi.org\/10.1007\/s13760-017-0816-5","journal-title":"Acta Neurol Belg"},{"key":"5864_CR57","unstructured":"U. Food and D. Administration (ed) (2025) FDA clears first blood test used in diagnosing Alzheimer\u2019s disease. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-clears-first-blood-test-used-diagnosing-alzheimers-disease"},{"issue":"4","key":"5864_CR58","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1038\/s41591-024-02869-z","volume":"30","author":"NR Barth\u00e9lemy","year":"2024","unstructured":"Barth\u00e9lemy NR et al (2024) Highly accurate blood test for Alzheimer\u2019s disease is similar or superior to clinical cerebrospinal fluid tests. Nat Med 30(4):1085\u20131095. https:\/\/doi.org\/10.1038\/s41591-024-02869-z","journal-title":"Nat Med"},{"issue":"7","key":"5864_CR59","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/s41582-024-00977-5","volume":"20","author":"SE Schindler","year":"2024","unstructured":"Schindler SE et al (2024) Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer\u2019s Disease. Nat Rev Neurol 20(7):426\u2013439. https:\/\/doi.org\/10.1038\/s41582-024-00977-5","journal-title":"Nat Rev Neurol"},{"key":"5864_CR60","doi-asserted-by":"publisher","unstructured":"Schindler SE et al (2024) Head-to-head comparison of leading blood tests for Alzheimer's disease pathology.\u00a0medRxiv. https:\/\/doi.org\/10.1101\/2024.06.12.24308839.\u00a0(in eng)","DOI":"10.1101\/2024.06.12.24308839"},{"issue":"3","key":"5864_CR61","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70038","volume":"21","author":"J Wang","year":"2025","unstructured":"Wang J et al (2025) Diagnostic accuracy of plasma p-tau217\/A\u03b242 for Alzheimer\u2019s disease in clinical and community cohorts. Alzheimers Dement 21(3):e70038. https:\/\/doi.org\/10.1002\/alz.70038","journal-title":"Alzheimers Dement"},{"issue":"1","key":"5864_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01555-z","volume":"16","author":"AH Dyer","year":"2024","unstructured":"Dyer AH et al (2024) Performance of plasma p-tau217 for the detection of amyloid-\u03b2 positivity in a memory clinic cohort using an electrochemiluminescence immunoassay. Alzheimers Res Ther 16(1):186. https:\/\/doi.org\/10.1186\/s13195-024-01555-z","journal-title":"Alzheimers Res Ther"},{"issue":"2","key":"5864_CR63","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14458","volume":"21","author":"M Khalafi","year":"2025","unstructured":"Khalafi M et al (2025) Diagnostic accuracy of phosphorylated tau217 in detecting Alzheimer\u2019s disease pathology among cognitively impaired and unimpaired: a systematic review and meta-analysis. Alzheimers Dement 21(2):e14458. https:\/\/doi.org\/10.1002\/alz.14458","journal-title":"Alzheimers Dement"},{"issue":"6","key":"5864_CR64","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/s1474-4422(21)00066-1","volume":"20","author":"B Dubois","year":"2021","unstructured":"Dubois B et al (2021) Clinical diagnosis of Alzheimer\u2019s disease: recommendations of the International Working Group. Lancet Neurol 20(6):484\u2013496. https:\/\/doi.org\/10.1016\/s1474-4422(21)00066-1","journal-title":"Lancet Neurol"},{"issue":"7","key":"5864_CR65","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70535","volume":"21","author":"S Palmqvist","year":"2025","unstructured":"Palmqvist S et al (2025) Alzheimer\u2019s association clinical practice guideline on the use of blood-based biomarkers in the diagnostic workup of suspected Alzheimer\u2019s disease within specialized care settings. Alzheimers Dement 21(7):e70535. https:\/\/doi.org\/10.1002\/alz.70535","journal-title":"Alzheimers Dement"},{"key":"5864_CR66","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12081836","author":"R Lai","year":"2024","unstructured":"Lai R, Li B, Bishnoi R (2024) P-tau217 as a reliable blood-based marker of Alzheimer\u2019s disease. Biomedicines. https:\/\/doi.org\/10.3390\/biomedicines12081836","journal-title":"Biomedicines"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05864-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-05864-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05864-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:26:42Z","timestamp":1777858002000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-05864-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5864"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-05864-2","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human Ethics and Consent to Participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"606"}}