@article{6191d34ac8ae4f56903f28484b72a4c2,
title = "Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography",
abstract = "Background: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. Objective Spinocerebellar ataxia type 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. Methods: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18F-SynVesT-1 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. Results: 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-operative Ataxia Rating Scale: ρ ranging from −0.467 to −0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from −0.465 to −0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. Conclusions: 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.",
keywords = "PET, SCA3, SV2A, clinical biomarker, synaptic loss",
author = "Zhao Chen and Guang Liao and Na Wan and Zhiyou He and Daji Chen and Zhichao Tang and Zhe Long and Guangdong Zou and Linliu Peng and Linlin Wan and Chunrong Wang and Huirong Peng and Yuting Shi and Yongxiang Tang and Jian Li and Yulai Li and Tingting Long and Xuan Hou and Lang He and Rong Qiu and Dengming Chen and Junling Wang and Jifeng Guo and Lu Shen and Yiyun Huang and Tetsuo Ashizawa and Thomas Klockgether and Beisha Tang and Ming Zhou and Shuo Hu and Hong Jiang",
note = "Funding Information: This study was funded by the National Key R&D Program of China (2021YFA0805200 to H.J.), the National Natural Science Foundation of China (81974176 and 82171254 to H.J.; 81901169 to Z.C.; 91859207 and 81771873 to S.H.; 81901305 to C.W.), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (2020JJ1008 to H.J.), the Science and Technology Innovation Group of Hunan Province (2020RC4043 to H.J.), the Scientific Research Foundation of Health Commission of Hunan Province (B2019183 to H.J.), the Key Research and Development Program of Hunan Province (2020SK2064 to H.J.), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H.J., the Natural Science Foundation of Hunan Province (2022JJ20094 and 2021JJ40974 to Z.C.; 2020JJ5925 to C.W.; 2022JJ40783 to L.H.; 2022JJ40703 to Z.L.), Science and Technology Innovation Team Talent Project of Hunan Province (2021RC4056 to S.H.); the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, 2020LNJJ12 to H.J. and 2020LNJJ01 to S.H.), the Central South University Research Programme of Advanced Interdisciplinary Study (2023QYJC010 to H.J.) and the Science and Technology Innovation Program of Hunan Province (2022RC1027 to Z.C.). Funding agencies: Funding Information: T.K. has received research support from the Bundesministerium f{\"u}r Bildung und Forschung (BMBF) and the National Institutes of Health (NIH). T.K. has received consultancy honoraria from Biogen, UCB, and Vico Therapeutics. T.A. has received grant from the NIH (NS104326). Relevant conflicts of interest/financial disclosures: Publisher Copyright: {\textcopyright} 2023 International Parkinson and Movement Disorder Society.",
year = "2023",
doi = "10.1002/mds.29395",
language = "English (US)",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "Wiley",
}