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In this study, we compared the performance of new commercially available plasma p-Tau217 assay developed by ALZpath to other established p-Tau assays in an autopsy-confirmed sample. We included 72 participants from the Arizona Study of Aging and Neurodegenerative Disorders cohort, with antemortem plasma assessments and postmortem neuropathological examination. Plasma p-Tau217 was measured using the single molecule arrays (SIMOA)-based ALZpath immunoassay and plasma p-Tau217 and p-Tau181 were analyzed with mesoscale discovery (MSD)-based immunoassays developed by Lilly Research Laboratories. Plasma biomarkers were compared with densities of post-mortem-assessed amyloid plaques and neurofibrillary changes. Levels of p-Tau217<jats:sub>ALZpath<\/jats:sub>, p-Tau217<jats:sub>Lilly<\/jats:sub> and p-Tau181<jats:sub>Lilly<\/jats:sub> were significantly associated with plaque (partial Spearman \u03c1\u2009=\u20090.58, \u03c1\u2009=\u20090.78, \u03c1\u2009=\u20090.65; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and neurofibrillary (\u03c1\u2009=\u20090.26, \u03c1\u2009=\u20090.51, \u03c1\u2009=\u20090.37; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) density scores, adjusting for age, sex, and time of interval between blood sampling and death. All three biomarkers were also significantly associated with plaque density scores (p-Tau217<jats:sub>ALZpath<\/jats:sub>, \u03c1\u2009=\u20090.53; p-Tau217<jats:sub>Lilly<\/jats:sub>, \u03c1\u2009=\u20090.73; p-Tau181<jats:sub>Lilly<\/jats:sub>, \u03c1\u2009=\u20090.59; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), when additionally adjusting for neurofibrillary density scores. However, only p-Tau217<jats:sub>Lilly<\/jats:sub> was significantly associated with neurofibrillary density scores (\u03c1\u2009=\u20090.32, <jats:italic>p<\/jats:italic>\u2009=\u20090.022), when adjusting for plaque density scores. The correlations of p-Tau217<jats:sub>ALZpath<\/jats:sub> and p-Tau181<jats:sub>Lilly<\/jats:sub> with plaque density scores were comparable, whereas p-Tau217<jats:sub>Lilly<\/jats:sub> exhibited significantly higher correlations with plaques (p<jats:sub>diff<\/jats:sub>\u22640.015) and neurofibrillary changes (p<jats:sub>diff<\/jats:sub>\u22640.004) than p-Tau217<jats:sub>ALZpath<\/jats:sub>. While p-Tau217<jats:sub>ALZpath<\/jats:sub> and p-Tau181<jats:sub>Lilly<\/jats:sub> predicted the presence of Alzheimer\u2019s disease neuropathological change (ADNC), Braak staging (Braak 0-IV vs. Braak V-VI) and CERAD neuritic plaque classification (low\/sparse vs. moderate\/frequent) with similar accuracies (area under the curve [AUC]<jats:sub>range<\/jats:sub>, 0.74\u20130.79), p-Tau217<jats:sub>Lilly<\/jats:sub> AUCs were significantly higher (AUC<jats:sub>range<\/jats:sub>,0.82\u20130.89, p<jats:sub>diff<\/jats:sub>\u22640.024) than the AUCs of p-Tau217<jats:sub>ALZpath<\/jats:sub>. In conclusion, p-Tau217<jats:sub>ALZpath<\/jats:sub> exhibited similar performance as p-Tau181<jats:sub>Lilly<\/jats:sub> but its correlations with core measures of AD pathology were significantly lower in comparison with p-Tau217<jats:sub>Lilly<\/jats:sub>. Future studies are warranted to replicate these findings in larger independent cohorts.<\/jats:p>","DOI":"10.1186\/s40478-025-02064-2","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T09:05:34Z","timestamp":1751274334000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparison of plasma ALZpath p-Tau217 with Lilly p-Tau217 and p-Tau181 in a neuropathological cohort"],"prefix":"10.1186","volume":"13","author":[{"given":"Divya","family":"Bali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Salvad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Atri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Reiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Jeromin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"issue":"1","key":"2064_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M et al (2023) Lecanemab in early alzheimer\u2019s disease. 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The operations of the Brain and Body Donation Program are approved by Institutional Review Boards and all participants, or their legal representatives gave informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and participant consent"}},{"value":"Figure 1 is original and created using BioRender.com.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DB, GS, SJ report no disclosures. OH is a part-time employee of Eli Lilly, and he has previously acquired research support (for Lund University) from AVID Radiopharmaceuticals, Biogen, C2N Diagnostics, Eli Lilly, Eisai, Fujirebio, GE Healthcare, and Roche. In the past 2 years, he has received consultancy\/speaker fees from Alzpath, BioArctic, Biogen, Bristol Meyer Squibb, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. TGB received paid consultancy from Biogen, Acadia Pharmaceuticals and Aprinoia Therapeutics; and has stock options with Vivid Genomics; and received honoraria from the NIH, Mayo Clinic, Stanford University, IOS Press\u2013 Journal of Parkinson\u2019s Disease and the International Movement Disorders Association. AJ is a Founder\/ CSO to Atlantic Biomarkers, LLC and has stock options with ALZpath. EMR is a cofounder and advisor of AlzPath, and a compensated scientific advisor to Alzheon, Denali, Enigma, Cognition Therapeutics, Retromer Therapeutics, and Vaxxinity.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"144"}}