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Cryo-electron microscopic (cryo-EM) studies have demonstrated that tau filaments extracted from tauopathy brains are characteristic of the disease and share a common fold(s) in the same disease group. Furthermore, the tau PTM profile changes during tau pathology formation and disease progression, and disease-specific PTMs are detected in and around the filament core. In addition, templated seeding has been suggested to trigger pathological tau amplification and spreading in vitro and in vivo, although the molecular mechanisms are not fully understood. Recently, we reported that the cryo-EM structures of tau protofilaments in SH-SY5Y cells seeded with patient-derived tau filaments show a core structure(s) resembling that of the original seeds. Here, we investigated PTMs of tau filaments accumulated in the seeded cells by liquid chromatography\/tandem mass spectrometry and compared them with the PTMs of patient-derived tau filaments. Examination of insoluble tau extracted from SH-SY5Y cells showed that numerous phosphorylation, deamidation and oxidation sites detected in the fuzzy coat in the original seeds were well reproduced in SH-SY5Y cells. Moreover, templated tau filament formation preceded both truncation of the N-\/C-terminals of tau and PTMs in and around the filament core, indicating these PTMs may predominantly be introduced after the degradation of the fuzzy coat.<\/jats:p>","DOI":"10.1093\/brain\/awad272","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T12:53:52Z","timestamp":1691585632000},"page":"4988-4999","source":"Crossref","is-referenced-by-count":17,"title":["Distinct tau folds initiate templated seeding and alter the post-translational modification profile"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3835-9070","authenticated-orcid":false,"given":"Airi","family":"Tarutani","sequence":"first","affiliation":[{"name":"Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science , Tokyo 156-8506 , Japan"},{"name":"Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The 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Institute for Medical Science of Aging, Aichi Medical University , Aichi 480-1195 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-7728","authenticated-orcid":false,"given":"Andrew C","family":"Robinson","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Neuroscience, The University of Manchester, Salford Royal Hospital , Salford M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M A","family":"Mann","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Neuroscience, The University of Manchester, Salford Royal Hospital , Salford M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Murayama","sequence":"additional","affiliation":[{"name":"Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Institute of Geratrics and Gerontology , Tokyo 173-0015 , Japan"},{"name":"Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Osaka University , Osaka 565-0871 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-5943","authenticated-orcid":false,"given":"Taisuke","family":"Tomita","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-8159","authenticated-orcid":false,"given":"Masato","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical Science , Tokyo 156-8506 , 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