{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:17:47Z","timestamp":1787735867519,"version":"build-2784847793"},"posted":{"date-parts":[[2024,7,5]]},"group-title":"Geriatric Medicine","reference-count":47,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer\u2019s disease (AD) pathology. 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 cerebrospinal fluid (CSF) biomarker tests.<\/jats:p>\n                <jats:p>\n                  Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  ]and p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  ) as well as with immunoassays (p-tau217\n                  <jats:sub>Lilly<\/jats:sub>\n                  , p-tau217\n                  <jats:sub>Janssen<\/jats:sub>\n                  , p-tau217\n                  <jats:sub>ALZpath<\/jats:sub>\n                  ). CSF biomarkers included p-tau217\n                  <jats:sub>Lilly<\/jats:sub>\n                  , and the FDA-approved p-tau181\/A\u03b242\n                  <jats:sub>Elecsys<\/jats:sub>\n                  and p-tau181\n                  <jats:sub>Elecsys<\/jats:sub>\n                  .\n                <\/jats:p>\n                <jats:p>\n                  All plasma p-tau217 tests exhibited high ability to detect abnormal A\u03b2-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  had the highest performance, with significantly higher AUCs than all the immunoassays (\n                  <jats:italic>P<\/jats:italic>\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.007). For detecting A\u03b2-PET status, %p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217\n                  <jats:sub>Lilly<\/jats:sub>\n                  and plasma p-tau217\n                  <jats:sub>ALZpath<\/jats:sub>\n                  had higher AUCs than plasma p-tau217\n                  <jats:sub>Janssen<\/jats:sub>\n                  for A\u03b2-PET status (\n                  <jats:italic>P<\/jats:italic>\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.006), and p-tau217\n                  <jats:sub>Lilly<\/jats:sub>\n                  outperformed plasma p-tau217\n                  <jats:sub>ALZpath<\/jats:sub>\n                  for tau-PET status (\n                  <jats:italic>P<\/jats:italic>\n                  <jats:sub>diff<\/jats:sub>\n                  =0.025). Plasma %p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  exhibited higher associations with all PET load outcomes compared to immunoassays; baseline A\u03b2-PET load (R\n                  <jats:sup>2<\/jats:sup>\n                  : 0.72; immunoassays: 0.47-0.58; P\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.001), baseline tau-PET load (R\n                  <jats:sup>2<\/jats:sup>\n                  : 0.51; immunoassays: 0.38-0.45; P\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.001), longitudinal A\u03b2-PET load (R\n                  <jats:sup>2<\/jats:sup>\n                  : 0.53; immunoassays: 0.31-0.38; P\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.001) and longitudinal tau-PET load (R\n                  <jats:sup>2<\/jats:sup>\n                  : 0.50; immunoassays: 0.35-0.43; P\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.014). Among immunoassays, plasma p-tau217\n                  <jats:sub>Lilly<\/jats:sub>\n                  was more strongly associated with A\u03b2-PET load than plasma p-tau217\n                  <jats:sub>Janssen<\/jats:sub>\n                  (\n                  <jats:italic>P<\/jats:italic>\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.020) and with tau-PET load than both plasma p-tau217\n                  <jats:sub>Janssen<\/jats:sub>\n                  and plasma p-tau217\n                  <jats:sub>ALZpath<\/jats:sub>\n                  (all\n                  <jats:italic>P<\/jats:italic>\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination[MMSE]) than all immunoassays (R\n                  <jats:sup>2<\/jats:sup>\n                  %p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  : 0.33; immunoassays: 0.27-0.30;\n                  <jats:italic>P<\/jats:italic>\n                  <jats:sub>diff<\/jats:sub>\n                  &lt;0.024). The main results were replicated in an external cohort from Washington University in St Louis (\n                  <jats:italic>n<\/jats:italic>\n                  =219). Finally, p-tau217\n                  <jats:sub>Nulisa<\/jats:sub>\n                  showed similar performance to other immunoassays in subsets of both cohorts.\n                <\/jats:p>\n                <jats:p>\n                  In summary, both MS-and immunoassay-based p-tau217 tests generally perform well in identifying A\u03b2-PET, tau-PET, and cognitive abnormalities, but %p-tau217\n                  <jats:sub>WashU<\/jats:sub>\n                  performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be better suited as triage tests where positive results are confirmed with a second test.\n                <\/jats:p>","DOI":"10.1101\/2024.07.02.24309629","type":"posted-content","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T12:40:15Z","timestamp":1720183215000},"source":"Crossref","is-referenced-by-count":14,"title":["A Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0557-5102","authenticated-orcid":false,"given":"No\u00eblle","family":"Warmenhoven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Salvad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Mattsson-Carlgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Bali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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