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Plasma p-tau212 is a novel blood biomarker that can discriminate cognitively unimpaired (CU) and subjective cognitive decline patients from mild cognitive impairment (MCI)-AD and AD dementia patients in clinical cohorts. Using Simoa technology, we evaluated plasma p-tau212 for its ability to detect emerging amyloid-beta (A\u03b2) pathology in CU individuals with brain amyloidosis from CSF A\u03b242\/40 ratio (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009317) or A\u03b2 PET scans (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009277). We benchmarked plasma p-tau212 against p-tau181, p-tau217, and p-tau231 by comparing their accuracies and fold changes for detecting brain amyloidosis. Our results showed that all the plasma p-tau biomarkers are increased in the CU CSF A\u03b2\u2009+\u2009participants, with the highest median fold change observed for plasma p-tau212. Discrimination performance of the biomarkers to differentiate amyloid PET-positive from amyloid PET-negative participants differed between plasma p-tau biomarkers, being higher for plasma p-tau217 and p-tau212 compared to plasma p-tau181 and p-tau231. Furthermore, plasma p-tau212 was elevated in participants with low A\u03b2 burden (CSF A\u03b2-positive, amyloid PET-negative), supporting its potential as a cost-effective, easily implemented biomarker for trial recruitment in early stages. Its further increase in A\u03b2 PET-positive participants suggests additional utility for monitoring anti-amyloid therapies.\n                  <\/jats:p>","DOI":"10.1007\/s00415-025-13572-5","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T15:44:49Z","timestamp":1766677489000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-\u03b2 pathology"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5083-0924","authenticated-orcid":false,"given":"Przemys\u0142aw R.","family":"Kac","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armand","family":"Gonz\u00e1lez-Escalante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mil\u00e0-Alom\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahnaz","family":"Shekari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Ortiz-Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Turton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Domingo","family":"Gispert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K.","family":"Karikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Su\u00e1rez-Calvet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"13572_CR1","unstructured":"O. of the Commissioner (2024) FDA Grants Accelerated approval for Alzheimer\u2019s Drug. 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HZ has served on scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, and has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD. KB has served as a consultant or on advisory boards for Abcam, Axon, BioArctic, Biogen, JOMDD\/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers. HZ and KB 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. MSC has received in the past 36mo consultancy\/speaker fees (paid to the institution) from Almirall, Eli Lilly, Quanterix, Novo Nordisk, and Roche Diagnostics. He has received consultancy fees or served on advisory boards (paid to the institution) of Eli Lilly, Grifols, Novo Nordisk, and Roche Diagnostics. He was granted a project and is a site investigator of a clinical trial (funded to the institution) by Roche Diagnostics. In-kind support for research (to the institution) was received from ADx Neurosciences, Alamar Biosciences, ALZPath, Avid Radiopharmaceuticals, Eli Lilly, Fujirebio, Janssen Research & Development, Meso Scale Discovery, and Roche Diagnostics; MSC did not receive any personal compensation from these organizations or any other for-profit organization. JDG has received research support from GE Healthcare, Roche Diagnostics, and Hoffmann-La Roche; has given lectures in symposia sponsored by General Electric, Philips, Life Molecular Imaging, and Biogen; has served on scientific advisory boards for Prothena and as a consultant for Roche Diagnostics; and is the inventor, founder, and co-owner of BetaScreen. The other authors declare that there are no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"48"}}