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due to tau (FTLD-tau)\u2014we compared cerebrospinal fluid (CSF) biomarkers of phosphorylated-tau (p-tau) p-tau181, p-tau212, tau368, total tau (t-tau), and the tau368\/t-tau ratio, and tested differentiation from non-tau (FTLD-TDP, neuronal \u03b1-synuclein disease (\u03b1Syn), and controls). In AD, CSF p-tau181 and p-tau212 were significantly higher than in all other groups, including FTLD-tau, while tau368\/t-tau was significantly lower. With the aim to combine tau phosphorylation biomarkers (p-tau181 and p-tau212) with biomarkers for severity of tau pathology (tau368), we made ratios between these biomarkers and examined their diagnostic accuracy in FTLD after excluding high\/intermediate AD neuropathologic change (ADNC). CSF p-tau181 and p-tau212, as well as p-tau181\/tau368 and p-tau212\/tau368, were higher in FTLD-tau compared with non-tau groups, and the diagnostic accuracy to discriminate FTLD-tau from FTLD-TDP improved. Levels of the ratios were increased in behavioral and primary progressive aphasia variants of tauopathies when compared to FTLD-TDP. Furthermore, the biomarkers showed significant correlation with both FTLD-tau and AD tau burden at autopsy across brain regions. These results suggest unique patterns of increased relative levels of p-tau epitopes in CSF among ADNC and FTLD-tau could improve the diagnosis of tauopathies and inform inclusion criteria in clinical trial design.<\/jats:p>","DOI":"10.1007\/s00401-026-03042-1","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T09:14:30Z","timestamp":1782292470000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tau368 improves p-tau diagnostic accuracy for FTLD-tau from FTLD-TDP"],"prefix":"10.1007","volume":"151","author":[{"given":"Przemys\u0142aw R.","family":"Kac","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katheryn A. 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HZ 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). PRK received royalties from Bioventix Plc (outside submitted work). KB has during 2023\u20132025 served as a consultant, at advisory boards, and has given lectures, produced educational materials and participated in educational programs for AC Immune, ALZPath, AriBio, Beckman-Coulter, BioArctic, Eisai, Lilly, Neurimmune, Novartis, Roche Diagnostics, Sunbird Bio, and Siemens Healthineers; all before Sept 2025, and is since Sept 2025 an employee of Lilly. KB 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 paper. DJI receives research funding paid to the institution for clinical trials by Alector, Cervo Med, Denali, Passage Bio and Prevail. DJI has unpaid positions on the scientific advisory board for the LBDA, the medical advisory board for the Association for Frontotemporal Degeneration and the board of directors for the International Society for Frontotemporal Dementias. EBL received consulting fees from Eli Lilly. The other authors declare no competing interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"71"}}