{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:11:04Z","timestamp":1790305864837,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Rainwater Foundation Tau Consortium"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R56AG061196"],"award-info":[{"award-number":["R56AG061196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RF1AG059789"],"award-info":[{"award-number":["RF1AG059789"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RF1AG058674"],"award-info":[{"award-number":["RF1AG058674"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30AG062421"],"award-info":[{"award-number":["P30AG062421"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["B.T.H."],"award-info":[{"award-number":["B.T.H."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","award":["2018-AARF-591935"],"award-info":[{"award-number":["2018-AARF-591935"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Martin L. and Sylvia Seevak Hoffman Fellowship for Alzheimer\u2019s Research","award":["U01 5U01NS110438-02"],"award-info":[{"award-number":["U01 5U01NS110438-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aggregation prone molecules, such as tau, form both historically well characterized fibrillar deposits (neurofibrillary tangles) and recently identified phosphate-buffered saline (PBS) extract species called proteopathic seeds. Both can cause normal endogenous tau to undergo templated misfolding. The relationship of these seeds to the fibrils that define tau-related diseases is unknown. We characterized the aqueous extractable and sarkosyl insoluble fibrillar tau species derived from human Alzheimer brain using mass spectrometry and in vitro bioassays. Post-translational modifications (PTMs) including phosphorylation, acetylation and ubiquitination are identified in both preparations. PBS extract seed competent tau can be distinguished from sarkosyl insoluble tau by the presence of overlapping, but less abundant, PTMs and an absence of some PTMs unique to the latter. The presence of ubiquitin and other PTMs on the PBS-extracted tau species correlates with the amount of tau in the seed competent size exclusion fractions, with the bioactivity and with the aggressiveness of clinical disease. These results demonstrate that the PTMs present on bioactive, seed competent PBS extract tau species are closely related to, but distinct from, the PTMs of mature paired helical filaments, consistent with the idea that they are a forme fruste of tau species that ultimately form fibrils.<\/jats:p>","DOI":"10.1093\/brain\/awad378","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T17:46:52Z","timestamp":1705600012000},"page":"637-648","source":"Crossref","is-referenced-by-count":21,"title":["Alzheimer proteopathic tau seeds are biochemically a <i>forme fruste<\/i> of mature paired helical filaments"],"prefix":"10.1093","volume":"147","author":[{"given":"Mukesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9","family":"Quittot","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-341X","authenticated-orcid":false,"given":"Simon","family":"Dujardin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph N","family":"Schlaffner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Viode","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Pathology, Boston Children\u2019s Hospital , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Wiedmer","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Beerepoot","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua E","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calina","family":"Glynn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-7806","authenticated-orcid":false,"given":"Analiese R","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Donahue","sequence":"additional","affiliation":[{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-0772","authenticated-orcid":false,"given":"Judith A","family":"Steen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7959-9401","authenticated-orcid":false,"given":"Bradley T","family":"Hyman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital , Boston, MA 02129 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"2024020201472972200_awad378-B1","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1002\/1873-3468.13108","article-title":"Tau filaments in neurodegenerative diseases","volume":"592","author":"Goedert","year":"2018","journal-title":"FEBS 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