{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T06:03:34Z","timestamp":1785045814044,"version":"3.55.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["AG073236"],"award-info":[{"award-number":["AG073236"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014269","name":"Philippe Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007457","name":"JPB Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016608","name":"Rainwater Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020398","name":"Fondation Philippe Chatrier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020398","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While it is clear that abnormal tau structures contribute to the clinical symptoms of Alzheimer's disease (AD), which of the many structural entities found in the AD brain underlie templated misfolding and progression of disease remains uncertain. However, their identification is crucial to target for more effective diagnostics and therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify the most pathogenic tau species driving Alzheimer's disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared the biochemical and templated seeding properties of tau isolated from post-mortem brain tissue of patients with varying rates of clinical progression, categorized as rapid, slow, or typical, based on longitudinal decline in cognitive performance assessed by Clinical Dementia Rating Sum of Boxes scores. Sarkosyl-insoluble filamentous preparations were compared to aqueous-soluble preparations. Focusing on the aqueous-soluble proteins, we further characterized the most efficient seeding species using size-exclusion chromatography and quantifying oligomers using dot blot under both native and denaturing conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A rapidly progressive course corresponded to enhanced tau seeding behavior, with the strongest correlations observed in the aqueous-soluble fraction. Using size-exclusion chromatography, we demonstrated that the seeding activity of fractions containing oligomers, correlated most strongly with disease aggressiveness. Moreover, quantifying oligomers using dot blot under both native and denaturing conditions, we found that rapid progressors had higher levels of oligomeric tau, which was also more stable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Aqueous-soluble oligomeric tau species may be an important driver of AD progression. Substantial heterogeneity was observed even in purified samples, suggesting that variations in tau conformers among patients may contribute to differences in clinical disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251400798","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T09:31:07Z","timestamp":1766395867000},"page":"864-875","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Seed-competent tau oligomers\u2019 activity correlates with the rate of progression in sporadic Alzheimer's disease patients"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5974-4061","authenticated-orcid":false,"given":"Romain","family":"Perbet","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Harvard Medical School, Cambridge, MA, USA"},{"name":"Present address: Institute of Pathology and Neuropathology, Hospices Civils de Lyon, France"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E","family":"Wiedmer","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"},{"name":"Present address: Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noe","family":"Quitot","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Harvard Medical School, Cambridge, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshil","family":"Bhavsar","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Perrin","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Harvard Medical School, Cambridge, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Gaona","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"},{"name":"Present address: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasie","family":"Mate de Gerando","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Harvard Medical School, Cambridge, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Gomez Isla","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Harvard Medical School, Cambridge, MA, USA"},{"name":"Massachusetts Alzheimer's Disease Research Center, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P","family":"Frosch","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Department of Neurology, Boston, MA, USA"},{"name":"Harvard 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