{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:00:24Z","timestamp":1791892824973,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230039"],"award-info":[{"award-number":["82230039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371349"],"award-info":[{"award-number":["82371349"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371879"],"award-info":[{"award-number":["82371879"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U21A20360"],"award-info":[{"award-number":["U21A20360"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Advancements in disease\u2010modifying therapies for spinocerebellar ataxia Type 3 (SCA3) underscore the need for robust biomarkers to monitor disease progression and evaluate treatment efficacy. Although motor phenotypes have been well characterized, less is known about non\u2010motor and imaging\u2010based features across different disease stages. This study aimed to characterize stage\u2010specific patterns of non\u2010motor and imaging biomarkers in SCA3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This cross\u2010observational study included 229 patients with SCA3 and 104 age\u2010 and sex\u2010matched healthy controls from the Organization for Southeast China for cerebellar ataxia research. Non\u2010motor symptoms were assessed using a battery of neuropsychological tests. Brain volume loss was assessed by 3.0\u2010Tesla MRI with regions\u2010of\u2010interest (ROI)\u2010based volumetric analysis. Neuroinflammation was quantified in\u00a0vivo using translocator protein positron emission tomography (TSPO\u2010PET) with the\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010DPA\u2010714 radioligand. Additive regression models were fitted to evaluate the cross\u2010sectional associations between biomarkers and disease stages. Receiver operating curve (ROC) analyses were applied to estimate the discriminative ability of the candidate biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Non\u2010motor symptoms, including cognitive functions, anxiety, fatigue, depression, and sleep quality, declined after ataxia onset in SCA3. Volume loss in the brainstem and ventral diencephalon diverged from normal controls at 0.7 and 0.2\u2009years before ataxia onset, respectively. Correspondingly, the TSPO signal in the brainstem and ventral diencephalon increased and deviated from normal throughout the disease course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our findings propose a staging model of SCA3 that includes a biomarker stage characterized by multidimensional objective indicators of neurodegeneration and neuroinflammation from pre\u2010ataxia to ataxia onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT04010214\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70555","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:13:09Z","timestamp":1791889989000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stage\u2010Specific Patterns of Imaging and Non\u2010Motor Biomarkers in Spinocerebellar Ataxia Type 3"],"prefix":"10.1002","author":[{"given":"Chun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Xian","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, Xinqiao Hospital and the Second Affiliated Hospital Army Medical University (Third Military Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2010Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou 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Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru\u2010Ying","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou 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of First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9472-8494","authenticated-orcid":false,"given":"Wan\u2010Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9655-9735","authenticated-orcid":false,"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2245-871X","authenticated-orcid":false,"given":"Shao\u2010Bo","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University  Fuzhou 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