{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:13:58Z","timestamp":1784859238510,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":69,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rossy Family Foundation"},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG080001"],"award-info":[{"award-number":["R01AG080001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Progressive supranuclear palsy is a neurodegenerative four-repeat tauopathy characterized by atypical parkinsonism and cognitive behavioural changes and a relatively uniform neuropathology. Building on prior identification of rare HLA (human leukocyte antigen) haplotypes in progressive supranuclear palsy, this study investigates whether these haplotypes correlate with distinct clinical and immunopathological phenotypes. In addition to retrospective collection of clinical data, we evaluated T and B cells, microglia and phosphorylated-tau (p-Tau) cytopathologies in 32 progressive supranuclear palsy cases. Machine learning was used to analyse whether pathological variables and their ratios, or the sequence of clinical symptoms are different HLA-defined groups, including one linked to narcolepsy (DRB1*15:01-DQB1*06:02). Neuropathology revealed regional differences in the severity of microglia load, density of cytotoxic T cells and p-Tau cytopathologies between groups. Machine learning revealed that specific ratios of neuroinflammatory markers reliably distinguished HLA haplotypes. Additionally, symptom progression sequences varied by HLA haplotype, suggesting a potential effect of neuroinflammatory profiles on disease trajectory. These findings support the notion that progressive supranuclear palsy pathology might be associated with various aetiological\u2013pathogenic events rarely including targetable autoimmune mechanisms as well. The HLA haplotype-dependent diversity of neuroinflammatory markers should be evaluated in clinical and biomarker studies in, and beyond, progressive supranuclear palsy to understand its relevance for patient stratification in disease modifying therapy trials.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag084","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:35:51Z","timestamp":1773146151000},"source":"Crossref","is-referenced-by-count":2,"title":["Distinct neuroinflammatory profiles in progressive supranuclear palsy associated with\n                    <i>HLA<\/i>\n                    haplotypes"],"prefix":"10.1093","volume":"8","author":[{"given":"Shelley L","family":"Forrest","sequence":"first","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Krembil Brain Institute, University Health Network , Toronto, Ontario M5T 0S8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah S","family":"Zaheer","sequence":"additional","affiliation":[{"name":"Rossy Centre for PSP, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Edmond J. Safra Program in Parkinson\u2019s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ain","family":"Kim","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetomo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Chasiotis","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan H","family":"Fox","sequence":"additional","affiliation":[{"name":"Rossy Centre for PSP, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Edmond J. Safra Program in Parkinson\u2019s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Division of Neurology, University of Toronto , Toronto, Ontario M5T 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Program, University Health Network , Toronto, Ontario M5G 2C4 ,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Carmela","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Krembil Brain Institute, University Health Network , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Rossy Centre for PSP, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Division of Neurology, University of Toronto , Toronto, Ontario M5T 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E","family":"Lang","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Krembil Brain Institute, University Health Network , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Rossy Centre for PSP, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Edmond J. Safra Program in Parkinson\u2019s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Division of Neurology, University of Toronto , Toronto, Ontario M5T 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"Gabor G","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Krembil Brain Institute, University Health Network , Toronto, Ontario M5T 0S8 ,","place":["Canada"]},{"name":"Rossy Centre for PSP, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Edmond J. Safra Program in Parkinson\u2019s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital , Toronto, Ontario M5T 2S8 ,","place":["Canada"]},{"name":"Division of Neurology, University of Toronto , Toronto, Ontario M5T 1A8 ,","place":["Canada"]},{"name":"Laboratory Medicine Program, University Health Network , Toronto, Ontario M5G 2C4 ,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"issue":"4","key":"2026041703580286300_fcag084-B1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s00401-022-02479-4","article-title":"Rainwater Charitable Foundation criteria for the neuropathologic diagnosis of progressive supranuclear palsy","volume":"144","author":"Roemer","year":"2022","journal-title":"Acta 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