{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:35:22Z","timestamp":1789450522032,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012736","name":"Institute on Aging, College of Medicine, University of Florida","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012736","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Alzheimer's disease neuropathologic change and alpha\u2010synucleinopathy commonly co\u2010exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta\u2010amyloid compared to alpha\u2010synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used digital histology to measure percent area\u2010occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha\u2010synucleinopathy, and a co\u2010pathology group with both Alzheimer's and alpha\u2010synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear\/logistic regression to compare groups and test the association between pathologies and clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were lower levels of tau pathology (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20091.86\u20132.96, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) across all tau antibodies in the co\u2010pathology group compared to the pure Alzheimer's pathology group. Among individuals with alpha\u2010synucleinopathy, higher alpha\u2010synuclein was associated with greater early tau (AT8 <jats:italic>\u03b2<\/jats:italic>\u2009=\u20091.37, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; MC1 <jats:italic>\u03b2<\/jats:italic>\u2009=\u20091.2, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) but not mature tau (TauC3 <jats:italic>p<\/jats:italic>\u2009=\u20090.18), whereas mature tau was associated with beta\u2010amyloid (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.21, <jats:italic>p<\/jats:italic>\u2009=\u20090.01). Finally, lower tau, particularly TauC3 pathology, was associated with lower frequency of both core clinical features and categorical clinical diagnosis of dementia with Lewy bodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Mature tau may be more closely related to beta\u2010amyloidosis than alpha\u2010synucleinopathy, and pathophysiological processes of tangle maturation may influence the clinical features of dementia in mixed Lewy\u2010Alzheimer's pathology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51988","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T07:50:20Z","timestamp":1706082620000},"page":"673-685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-9009","authenticated-orcid":false,"given":"Sanaz","family":"Arezoumandan","sequence":"first","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-2766","authenticated-orcid":false,"given":"Katheryn A.Q.","family":"Cousins","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"Ohm","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaKayla","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Gee","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0079-9441","authenticated-orcid":false,"given":"Jeffrey S.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey T.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia 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