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Dyer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Progressive supranuclear palsy (PSP) is typically characterized by vertical supranuclear gaze palsy and early falls, referred to as Richardson\u2019s syndrome (PSP-RS). Other presentations include postural instability (PSP-PI), Parkinsonism (PSP-P), speech\/language disorder (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). However, differences across the early presentations and their subsequent clinical courses remain to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to characterize early PSP subtypes and their subsequent progressions using a large postmortem dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An automated pipeline incorporating fine-tuned Chat Generative Pretrained Transformer (ChatGPT) was developed. The pipeline collected 195 clinical features with onset information from autopsy-confirmed PSP cases without significant neurodegenerative co-pathologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A structured clinicopathologic dataset from 588 patients was analyzed. The results from unsupervised clustering were distilled into a decision tree model. The mutually exclusive algorithm identified seven subtypes: PSP-PF (postural and frontal dysfunction), PSP-RS, PSP-PI, PSP-P, PSP-SL, PSP-F, and PSP-OM, based on five clinical manifestations: frontal presentation, postural instability, ocular motor dysfunction, speech\/language disorder, and Parkinsonism. PSP-PF showed rapid progression, the shortest median disease duration (six years), and high tau burden in cortical and subcortical regions. In PSP-F, frontal presentation preceded other symptoms by four years, with a nine-year disease duration\u2014second longest after PSP-P (10\u00a0years). PSP-CBS was not identified as an independent subtype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This data-driven study identified a novel, aggressive PSP phenotype characterized by early postural and frontal dysfunction. Early subtyping using the decision tree model would help clinicians estimate progression and facilitate early patient recruitment for clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-025-13459-5","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:10:10Z","timestamp":1760721010000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Early subtypes and progressions of progressive supranuclear palsy: a data-driven brain bank study"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-7355","authenticated-orcid":false,"given":"Daisuke","family":"Ono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Sekiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil B.","family":"Ghayal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia R.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanu F.","family":"Roemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Uitti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Litvan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Josephs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew K.","family":"Wszolek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"13459_CR1","first-page":"25","volume":"88","author":"JC Richardson","year":"1963","unstructured":"Richardson JC, Steele J, Olszewski J (1963) Supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia. 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Neuropathol Appl Neurobiol 40:149\u2013163","journal-title":"Neuropathol Appl Neurobiol"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13459-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-025-13459-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13459-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T01:05:46Z","timestamp":1761699946000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-025-13459-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["13459"],"URL":"https:\/\/doi.org\/10.1007\/s00415-025-13459-5","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"14 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"ZKW is partially supported by the NIH\/NIA and NIH\/NINDS (1U19AG063911, FAIN: U19AG063911), the Haworth Family Professorship in Neurodegenerative Diseases fund, The Albertson Parkinson\u2019s Research Foundation, and PPND Family Foundation. He serves as PI or Co-PI on Biohaven Pharmaceuticals, Inc. (BHV4157-206), Vigil Neuroscience, Inc. (VGL101-01.002, VGL101-01.201, Csf1r biomarker and repository project, and ultra-high field MRI in the diagnosis and management of CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia), ONO-2808-03, and Amylyx Pharmaceuticals, Inc. (A35-009) projects\/grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research and as an external advisory board member for the Vigil Neuroscience, Inc., and as a consultant for Eli Lilly & Company and Savanna Bio. KAJ is funded by the National Institute of Neurological Disorders and Stroke (R01- NS89757) and the National Institute on Deafness and Other Communication Disorders (R01-DC14942 & R01-DC12519).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"704"}}