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This study investigates the association of regional atrophy (structural MRI), neuroinflammation ([11C]-PK11195 PET), peripheral markers of neurodegeneration [plasma neurofilament light chain (NfL)] and clinical severity [PSP rating scale (PSPRS)] with survival in people with PSP. Fifty-nine people with PSP underwent longitudinal structural MRI, surviving on average 3.2 years from the first scan (MRI cohort). Sixteen participants (PET cohort) within this cohort underwent cross-sectional [11C]-PK11195 PET and blood sampling for plasma NfL. We applied modality-specific principal component analyses on imaging data and ran partial correlations, multivariate regressions and Bayesian models to evaluate the association between survival and imaging patterns, clinical severity and plasma NfL. In the PET cohort, higher levels of localized inflammation in subcortical regions [rho = \u22120.49, P = 0.02, Bayes factor (BF) = 8.07] and plasma NfL (rho = \u22120.57, P = 0.01, BF = 4.63) were associated with shorter survival, while PSPRS scores were not significant predictors of survival. Subcortical atrophy was associated with shorter survival in the larger cohort (r = \u22120.38, P = 0.001; \u03b2 = \u22120.66, P = 0.001). Spearman\u2019s correlations, multivariate regressions and Bayesian models converged to the same results. Regional subcortical atrophy is a robust biomarker associated with survival in people with PSP that can be utilized in large-scale clinical trials. Translocator protein (TSPO) PET and plasma NfL offer promising complementary markers for smaller-scale trials, where they may prove more sensitive than clinical scores or structural MRI alone. By linking neuroinflammation to survival, our results also highlight immunotherapy as a promising avenue for disease-modifying treatment in PSP.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf467","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:03:16Z","timestamp":1764162196000},"source":"Crossref","is-referenced-by-count":6,"title":["Inflammation PET and plasma neurofilament light predict survival in people with progressive supranuclear palsy"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-2747","authenticated-orcid":false,"given":"Noah L","family":"Shapiro","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"UK Dementia Research Institute at the University of Cambridge , Cambridge, CB2 0AH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Simon","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-8024","authenticated-orcid":false,"given":"Elijah","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, Addenbrooke\u2019s Hospital, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamen A","family":"Tsvetanov","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"Department of Psychology, University of Cambridge , Cambridge, CB2 3EB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Goddard","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"UK Dementia Research Institute at the University of Cambridge , Cambridge, CB2 0AH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davi S","family":"Vontobel","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"UK Dementia Research Institute at the University of Cambridge , Cambridge, CB2 0AH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-0117","authenticated-orcid":false,"given":"Robert","family":"Durcan","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3052-3879","authenticated-orcid":false,"given":"Leonidas","family":"Chouliaras","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, Addenbrooke\u2019s Hospital, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Fryer","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"Wolfson Brain Imaging Centre, University of Cambridge , Cambridge, CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young T","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"Wolfson Brain Imaging Centre, University of Cambridge , Cambridge, CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin","family":"Aigbirhio","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"Wolfson Brain Imaging Centre, University of Cambridge , Cambridge, CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute and Department of Neurodegenerative Disease at UCL , London, NW1 3BT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9736-2283","authenticated-orcid":false,"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich, 81377 ,","place":["Germany"]},{"name":"Institute for Stroke and Dementia Research (iSD), University Hospital, Ludwig-Maximilians-Universit\u00e4t , Munich, 81377 ,","place":["Germany"]},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg , M\u00f6lndal, 431 39 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9247-2843","authenticated-orcid":false,"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[{"name":"Munich Cluster for Systems Neurology (SyNergy) , Munich, 81377 ,","place":["Germany"]},{"name":"Institute for Stroke and Dementia Research (iSD), University Hospital, Ludwig-Maximilians-Universit\u00e4t , Munich, 81377 ,","place":["Germany"]},{"name":"Bavarian Cancer Research Center (BZKF), Partner Site Munich , Munich, 80539 ,","place":["Germany"]},{"name":"German Cancer Consortium (DKTK), Partner Site Munich, a partnership between German Cancer Research Center (DKFZ) and LMU Munich , Munich, 80366 ,","place":["Germany"]},{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich , Munich 81377 ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich , Munich, 81377 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute and Department of Neurodegenerative Disease at UCL , London, NW1 3BT ,","place":["UK"]},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg , M\u00f6lndal, 431 39 ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal, 405 30 ,","place":["Sweden"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53792 ,","place":["USA"]},{"name":"Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay , Hong Kong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0837-5080","authenticated-orcid":false,"given":"John T","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, Addenbrooke\u2019s Hospital, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"Cambridge University Hospitals NHS Foundation Trust , Cambridge, CB2 0QQ ,","place":["UK"]},{"name":"Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge , Cambridge, CB2 7EF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge, CB2 0SZ ,","place":["UK"]},{"name":"UK Dementia Research Institute at the University of Cambridge , Cambridge, CB2 0AH ,","place":["UK"]},{"name":"Cambridge University Hospitals NHS Foundation Trust , Cambridge, CB2 0QQ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"issue":"6","key":"2025121705563397900_fcaf467-B1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: The Movement Disorder 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