{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:12:04Z","timestamp":1785892324465,"version":"3.56.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Blood-based biomarkers, especially P-tau217, have been gaining interest as diagnostic tools to measure Alzheimer disease (AD) pathology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We developed a plasma P-tau217 chemiluminescent immunoassay using 4G10E2 and IBA493 as antibodies, a synthetic tau peptide as calibrator, and the Quanterix SP-X imager. Analytical validation performed in a College of American Pathologists-accredited CLIA laboratory involved multiple kit lots, operators, timepoints, and imagers. Florbetapir positron emission tomography was used to quantify amyloid for clinical validation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Precision across 80 runs was \u226420% CV using 23 patient-derived samples ranging from 0.09\u2005U\/mL to 3.35\u2005U\/mL. No significant lot-to-lot differences were observed. There was no interference from purified tau (2N4R) or lipemia, but hemolysis greater than 2 + was not acceptable. Functional analytical sensitivity (lower limit of quantitation) was 0.08\u2005U\/mL. Linearity studies support the use of a standard 1:2 plasma dilution. Samples demonstrated stability at 7 freeze\/thaw cycles, with room temperature and refrigerated stability established for up to 72\u2005hours. The final analytical measurement range was 0.08 to 2.81\u2005U\/mL. The calibration curve maintained \u226420% CV for raw signal intensity and 80% to 120% relative error for back-fitted concentration using a log-log power regression. Initial clinical assessment using plasma samples from 1091 individuals screened in TRAILBLAZER-ALZ 2 demonstrated an area under the curve of 91.6% (95% CI 0.90\u20130.94) with brain amyloid as the comparator. Positive and negative predictive value was &amp;gt;90% and &amp;gt;85%, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Through analytical validation, this assay demonstrated robust performance across multiple lots, operators, and instruments and could be used as a tool for diagnosing AD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jalm\/jfae155","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T16:28:24Z","timestamp":1737476904000},"page":"533-545","source":"Crossref","is-referenced-by-count":10,"title":["Analytical Validation and Performance of a Blood-Based P-tau217 Diagnostic Test for Alzheimer Disease"],"prefix":"10.1093","volume":"10","author":[{"given":"Adam","family":"Abel","sequence":"first","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Chambers","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Fill","sequence":"additional","affiliation":[{"name":"Work completed while an employee of Eli Lilly and Company"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Reiske","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lu","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Morris","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Faya","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose C","family":"Beck","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Pontecorvo","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C","family":"Collins","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E","family":"Schade","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Mintun","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E","family":"Hodsdon","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"2025050206372651500_jfae155-B1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in early symptomatic Alzheimer disease: the trailblazer-alz 2 randomized clinical trial","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"key":"2025050206372651500_jfae155-B2","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's association workgroup","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimers Dement"},{"key":"2025050206372651500_jfae155-B3","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1515\/cclm-2023-1434","article-title":"Blood-based biomarkers in Alzheimer's disease\u2014moving towards a new era of diagnostics","volume":"62","author":"Arslan","year":"2024","journal-title":"Clin Chem Lab Med"},{"key":"2025050206372651500_jfae155-B4","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"},{"key":"2025050206372651500_jfae155-B5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13195-022-01005-8","article-title":"Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217","volume":"14","author":"Groot","year":"2022","journal-title":"Alzheimers Res Ther"},{"key":"2025050206372651500_jfae155-B6","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1038\/s41467-020-15436-0","article-title":"Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer's disease","volume":"11","author":"Janelidze","year":"2020","journal-title":"Nat Commun"},{"key":"2025050206372651500_jfae155-B7","doi-asserted-by":"crossref","first-page":"e14022","DOI":"10.15252\/emmm.202114022","article-title":"Soluble p-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau","volume":"13","author":"Mattsson-Carlgren","year":"2021","journal-title":"EMBO Mol Med"},{"key":"2025050206372651500_jfae155-B8","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"},{"key":"2025050206372651500_jfae155-B9","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1093\/brain\/awaa329","article-title":"Plasma p-tau217: from \u2018new kid\u2019 to most promising candidate for Alzheimer's disease blood test","volume":"143","author":"Teunissen","year":"2020","journal-title":"Brain"},{"key":"2025050206372651500_jfae155-B10","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/s00415-023-12148-5","article-title":"Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort","volume":"271","author":"Mendes","year":"2024","journal-title":"J Neurol"},{"key":"2025050206372651500_jfae155-B11","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1093\/brain\/awac333","article-title":"Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer's disease","volume":"146","author":"Janelidze","year":"2023","journal-title":"Brain"},{"key":"2025050206372651500_jfae155-B12","first-page":"1797","article-title":"Plasma p-tau231 and p-tau217 as state markers of amyloid-beta pathology in preclinical Alzheimer's disease","volume":"28","author":"Mila-Aloma","year":"2022","journal-title":"Nat Med"},{"key":"2025050206372651500_jfae155-B13","author":"Quanterix"},{"key":"2025050206372651500_jfae155-B14","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13195-021-00939-9","article-title":"Clinical and analytical comparison of six simoa assays for plasma p-tau isoforms p-tau181, p-tau217, and p-tau231","volume":"13","author":"Bayoumy","year":"2021","journal-title":"Alzheimers Res Ther"},{"key":"2025050206372651500_jfae155-B15","doi-asserted-by":"crossref","first-page":"e14408","DOI":"10.15252\/emmm.202114408","article-title":"Blood-based biomarkers for Alzheimer's disease","volume":"14","author":"Leuzy","year":"2022","journal-title":"EMBO Mol Med"},{"key":"2025050206372651500_jfae155-B16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1056\/NEJMoa1705971","article-title":"Trial of solanezumab for mild dementia due to Alzheimer's disease","volume":"378","author":"Honig","year":"2018","journal-title":"N Engl J Med"},{"key":"2025050206372651500_jfae155-B17","volume-title":"CLSI EP15: User verification of precision and estimation of bias; approved guideline","author":"CLSI (Clinical and Laboratory Standards Institute)","year":"2012","edition":"3rd Ed"},{"key":"2025050206372651500_jfae155-B18","volume-title":"CLSI EP17-A2: Evaluation of detection capability for clinical laboratory measurement procedures; approved guideline","author":"CLSI (Clinical and Laboratory Standards Institute)","year":"2012","edition":"2nd Ed"},{"key":"2025050206372651500_jfae155-B19","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1001\/jamaneurol.2022.2793","article-title":"Association of amyloid reduction after donanemab treatment with tau pathology and clinical outcomes: the trailblazer-alz randomized clinical trial","volume":"79","author":"Shcherbinin","year":"2022","journal-title":"JAMA Neurol"},{"key":"2025050206372651500_jfae155-B20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v098.i11","article-title":"Cutpointr: improved estimation and validation of optimal cutpoints in r","volume":"98","author":"Thiele","year":"2021","journal-title":"J Stat Softw"},{"key":"2025050206372651500_jfae155-B21","volume-title":"Analytical validation and initial clinical evaluation of a new blood-based diagnostic test for Alzheimer\u2019s disease","author":"Schade","year":"2023"},{"key":"2025050206372651500_jfae155-B22","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\u2014recommendations from the global ceo initiative on Alzheimer's disease","volume":"20","author":"Schindler","year":"2024","journal-title":"Nat Rev Neurol"},{"key":"2025050206372651500_jfae155-B23","volume-title":"EP05-A3: Evaluation of precision of quantitative measurement procedures; approved guideline","author":"CLSI (Clinical and Laboratory Standards Institute)","year":"2012","edition":"3rd Ed"},{"key":"2025050206372651500_jfae155-B24","volume-title":"CLSI EP26: User evaluation of acceptability of a reagent lot change","author":"CLSI (Clinical and Laboratory Standards Institute)","year":"2022","edition":"2nd Ed"},{"key":"2025050206372651500_jfae155-B25","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's disease","volume":"20","author":"Gonzalez-Ortiz","year":"2024","journal-title":"Alzheimers Dement"},{"key":"2025050206372651500_jfae155-B26","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 abeta42\/40 ratio to identify presence of brain amyloid","volume":"20","author":"Meyer","year":"2024","journal-title":"Alzheimers Dement"},{"key":"2025050206372651500_jfae155-B27","doi-asserted-by":"crossref","first-page":"426","DOI":"10.14283\/jpad.2023.43","article-title":"Diagnostic biomarkers of amyloid and tau pathology in Alzheimer's disease: an overview of tests for clinical practice in the United States and Europe","volume":"10","author":"Iaccarino","year":"2023","journal-title":"J Prev Alzheimers Dis"},{"key":"2025050206372651500_jfae155-B28","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s43587-023-00403-3","article-title":"Blood biomarkers for Alzheimer's disease in clinical practice and trials","volume":"3","author":"Hansson","year":"2023","journal-title":"Nat Aging"},{"key":"2025050206372651500_jfae155-B29","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1002\/alz.12756","article-title":"The Alzheimer's association appropriate use recommendations for blood biomarkers in Alzheimer's disease","volume":"18","author":"Hansson","year":"2022","journal-title":"Alzheimers Dement"},{"key":"2025050206372651500_jfae155-B30","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"},{"key":"2025050206372651500_jfae155-B31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmsacl.2022.12.002","article-title":"The validity of laboratory developed tests: leave it to the experts?","volume":"27","author":"Marzinke","year":"2023","journal-title":"J Mass Spectrom Adv Clin Lab"},{"key":"2025050206372651500_jfae155-B32","author":"FDA"},{"key":"2025050206372651500_jfae155-B33","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1093\/jalm\/jfac075","article-title":"It's valid, but is it rational?","volume":"7","author":"Jones","year":"2022","journal-title":"J Appl Lab Med"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/10\/3\/533\/61529460\/jfae155.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/10\/3\/533\/61529460\/jfae155.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T10:37:42Z","timestamp":1746182262000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/10\/3\/533\/7965753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,1,21]]},"published-print":{"date-parts":[[2025,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jalm\/jfae155","relation":{},"ISSN":["2475-7241"],"issn-type":[{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2025,1,21]]}}}