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Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-\u03b2 (A\u03b2)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests.<\/jats:p>\n                  <jats:p>Samples from 998 individuals [mean (range) age 68.5 (20.0\u201392.5) years, 53% female] from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analysed. Plasma p-tau217 was measured with mass spectrometry assays [the ratio between phosphorylated and non-phosphorylated (%p-tau217WashU) and p-tau217WashU] and with immunoassays (p-tau217Lilly, p-tau217Janssen and p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, the US Food and Drug Administration-approved p-tau181\/A\u03b242Elecsys, and p-tau181Elecsys.<\/jats:p>\n                  <jats:p>All plasma p-tau217 tests exhibited a high ability to detect abnormal A\u03b2-PET [area under the curve (AUC) range: 0.91\u20130.96] and tau-PET (AUC range: 0.94\u20130.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff &amp;lt; 0.007). For detecting A\u03b2-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83\u20130.88), sensitivity of 0.91 (immunoassays: 0.84\u20130.87) and a specificity of 0.94 (immunoassays: 0.85\u20130.89). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for A\u03b2-PET status (Pdiff &amp;lt; 0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (Pdiff = 0.025). Plasma %p-tau217WashU exhibited stronger associations with all PET load outcomes compared with immunoassays; baseline A\u03b2-PET load (R2: 0.72; immunoassays: 0.47\u20130.58; Pdiff &amp;lt; 0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38\u20130.45; Pdiff &amp;lt; 0.001), longitudinal A\u03b2-PET load (R2: 0.53; immunoassays: 0.31\u20130.38; Pdiff &amp;lt; 0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35\u20130.43; Pdiff &amp;lt; 0.014). Among immunoassays, plasma p-tau217Lilly was more associated with A\u03b2-PET load than plasma p-tau217Janssen (Pdiff &amp;lt; 0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff &amp;lt; 0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination) than all immunoassays (R2: %p-tau217WashU: 0.33; immunoassays: 0.27\u20130.30; Pdiff &amp;lt; 0.024). The main results were replicated in an external cohort from Washington University in St Louis (n = 219). Finally, p-tau217NULISA showed similar performance to other immunoassays in subsets of both cohorts.<\/jats:p>\n                  <jats:p>In summary, both mass spectrometry- and immunoassay-based p-tau217 tests generally perform well in identifying A\u03b2-PET, tau-PET and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for Alzheimer\u2019s disease pathology, whereas some immunoassays might be better suited as triage tests where positive results are confirmed with a second test, which needs to be determined by future reviews incorporating results from multiple cohorts.<\/jats:p>","DOI":"10.1093\/brain\/awae346","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T07:14:45Z","timestamp":1729926885000},"page":"416-431","source":"Crossref","is-referenced-by-count":137,"title":["A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0557-5102","authenticated-orcid":false,"given":"No\u00eblle","family":"Warmenhoven","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University , Malm\u00f6 211 46 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