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Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202\/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-46876-7","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T07:02:40Z","timestamp":1711177360000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer\u2019s disease neuropathology"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5083-0924","authenticated-orcid":false,"given":"Przemys\u0142aw 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H.Z. has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche. K.B. has served as a consultant or at advisory boards for Abcam, Axon, BioArctic, Biogen, JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers. H.Z. and K.B. are co-founders of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. NJA has given lectures in symposia sponsored by Lilly, BioArctic, and Quanterix. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2615"}}