{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T03:05:49Z","timestamp":1780369549967,"version":"3.54.1"},"posted":{"date-parts":[[2025,7,5]]},"group-title":"Neurology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,4]]},"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). Differences across the early presentations and in their subsequent progression have yet 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 Pre-trained 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. After distilling results with unsupervised clustering, a decision tree model was developed. With five clinical manifestations: frontal presentation, postural instability, ocular motor dysfunction, speech\/language disorder, and parkinsonism, this 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. 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 years). 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 utilizing the decision tree model would help clinicians estimate progression and facilitate early patient recruitment for clinical trials.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.07.04.25330863","type":"posted-content","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T17:40:30Z","timestamp":1751737230000},"source":"Crossref","is-referenced-by-count":2,"title":["Early Subtypes and Progressions of Progressive Supranuclear Palsy: A Data-Driven Brain Bank Study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-7355","authenticated-orcid":false,"given":"Daisuke","family":"Ono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-5966","authenticated-orcid":false,"given":"Hiroaki","family":"Sekiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4398-7939","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-3445","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-1053","authenticated-orcid":false,"given":"Zbigniew K.","family":"Wszolek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-7917","authenticated-orcid":false,"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025090614250573000_2025.07.04.25330863v2.1","first-page":"25","article-title":"Supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia. 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