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All participants received SV2A\u2010PET imaging using <jats:sup>18<\/jats:sup>F\u2010SynVesT\u20101 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co\u2010operative Ataxia Rating Scale: \u03c1 ranging from \u22120.467 to \u22120.667, <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.002; Scale of Assessment and Rating of Ataxia: \u03c1 ranging from \u22120.465 to \u22120.586, <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. \u00a9 2023 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29395","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T14:44:45Z","timestamp":1680792285000},"page":"978-989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by <scp>SV2A<\/scp> Positron Emission Tomography"],"prefix":"10.1002","volume":"38","author":[{"given":"Zhao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of 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