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Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specific tau species became abnormal at different points along the disease continuum. Based on these findings, we developed a data-driven, blood-based staging model that demonstrated strong consistency across cohorts (&gt;85% agreement in \u226590% initializations) and reflected changes in other AD biomarkers. These plasma-based stages were associated with clinical diagnoses, positron emission tomography-based stages and distinct patterns of longitudinal disease progression, including A\u03b2- and tau-positron emission tomography uptake, atrophy and cognitive decline. This study highlights the potential of tau blood-based biomarkers for biological staging in AD, offering a scalable tool for tracking disease progression and guiding clinical decisions.\n                  <\/jats:p>","DOI":"10.1038\/s43587-025-00951-w","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T09:04:00Z","timestamp":1755853440000},"page":"2297-2308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Plasma tau biomarkers for biological staging of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7684-6318","authenticated-orcid":false,"given":"Laia","family":"Montoliu-Gaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-9230","authenticated-orcid":false,"given":"Gemma","family":"Salvad\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Therriault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-6060","authenticated-orcid":false,"given":"Johanna","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-8378","authenticated-orcid":false,"given":"Shorena","family":"Janelidze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2298-220X","authenticated-orcid":false,"given":"Sophia","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Benedet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Rahmouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-678X","authenticated-orcid":false,"given":"Juan","family":"Lantero-Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-7724","authenticated-orcid":false,"given":"Niklas","family":"Mattsson-Carlgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-1930","authenticated-orcid":false,"given":"Sebastian","family":"Palmqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6958-2393","authenticated-orcid":false,"given":"Gunnar","family":"Brinkmalm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stomrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-6193","authenticated-orcid":false,"given":"Johan","family":"Gobom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9116-1376","authenticated-orcid":false,"given":"Pedro","family":"Rosa-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-7286","authenticated-orcid":false,"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"951_CR1","doi-asserted-by":"crossref","unstructured":"2024 Alzheimer\u2019s disease facts and figures. 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G.S. has received speaker fees from Springer Nature, Esteve, GE Healthcare and Adium and has participated in advisory board for Johnson & Johnson. H.Z. has served at 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; has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche and WebMD; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). S.P. has acquired research support (for the institution) from Avid and ki elements through ADDF. In the past 2\u2009years, he has received consultancy\/speaker fees from BioArtic, Biogen, Esai, Eli Lilly, Novo Nordisk and Roche. K.B. has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD\/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this Article. P.R.-N. participated in advisory board for Roche, Novo Nordisk and Cerveau (outside submitted work). O.H. is an employee of Eli Lilly and Lund University, 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\u2009years, he has received consultancy\/speaker fees from ALZpath, BioArctic, Biogen, Bristol Myers Squibb, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. J.T. has served as a paid consultant for Neurotorium and for Alzheon Inc. P.R.-N. participated in advisory board for Roche, Novo Nordisk and Cerveau (outside submitted work). N.M.-C. has received consultancy\/speaker fees from Biogen, Merck and Owkin. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}