Dopaminergic Dysfunction and Glucose Metabolism Characteristics in Parkin-Induced Early-Onset Parkinson’s Disease Compared to Genetically Undetermined Early-Onset Parkinson’s Disease  

作　　者：Feng-Tao Liu Jia-Ying Lu Yi-Min Sun Ling Li Yu-Jie Yang Jue Zhao Jing-Jie Ge Ping Wu Jie-Hui Jiang Jian-Jun Wu Chuan-Tao Zuo Jian Wang 

机构地区：[1]Department of Neurology,National Clinical Research Center for Aging and Medicine&National Center for Neurological Disorders,Huashan Hospital,Fudan University,12 Wulumuqi Middle Road,Shanghai 200040,China [2]Department of Nuclear Medicine&PET Center,National Clinical Research Center for Aging and Medicine&National Center for Neurological Disorders,Huashan Hospital,Fudan University,518 East Wuzhong Road,Shanghai 200235,China [3]Institute of Biomedical Engineering,School of Life Sciences,Shanghai University,Shanghai 200444,China [4]Human Phenome Institute,Fudan University,Shanghai 200433,China

出　　处：《Phenomics》2023年第1期22-33,共12页表型组学（英文）

基　　金：the grants from Ministry of Science and Technology of China(No.2016YFC1306504);Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01);ZJLab,and National Nature Science Foundation of China(Nos.91949118,81771372);Chuan-Tao Zuo received the research funding from the National Natural Science Foundation of China(Nos.82021002,81971641,81671239,and 81361120393);Shanghai Municipal Science and Technology Major Project(No.2017SHZDZX01);Science and Technology Commission of Shanghai Municipality(Nos.19441903500 and 17JC1401600);Shanghai Aging and Maternal and Child Health Research Special Project(No.2020YJZX0111);Clinical Research Plan of Shanghai Hospital Development Center(No.SHDC2020CR1038B);Science and Technology Innovation 2030 Major Project(No.2022ZD0211600);Feng-Tao Liu received the grant of the National Nature Science Foundation of China(Nos.82171252,81701250).

摘　　要：While early-onset Parkinson’s disease(EOPD)caused by mutations in the parkin gene(PRKN)tends to have a relatively benign course compared to genetically undetermined(GU)-EOPD,the exact underlying mechanisms remain elusive.We aimed to search for the differences between PRKN-EOPD and GU-EOPD by dopamine transporter(DAT)and glucose metabolism positron-emission-tomography(PET)imaging.Twelve patients with PRKN-EOPD and 16 with GU-EOPD who accepted both ^(11)C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl)tropane(^(11)C-CFT)and ^(18)F-fluorodeoxyglucose PET were enrolled.The ^(11)C-CFT uptake was analyzed on both regional and voxel levels,whereas glucose metabolism was assessed in a voxel-wise fashion.Correlations between DAT and glucose metabolism imaging,DAT imaging and clinical severity,as well as glucose metabolism imaging and clinical severity were explored.Both clinical symptoms and DAT-binding pat-terns in the posterior putamen were highly symmetrical in patients with PRKN-EOPD,and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with PRKN-EOPD than GU-EOPD.Meanwhile,the DAT binding was associ-ated with the severity of motor dysfunction in patients with GU-EOPD only.Patients with PRKN-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus(supplementary motor area(SMA)),contralateral substantia nigra,contralateral thalamus,and contralateral cerebellum.Notably,glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen.Patients with PRKN-EOPD showed enhanced metabolic connectivity within the bilateral putamen,ipsilateral paracentral and precentral lobules,and the ipsilateral SMA.Collectively,compared to GU-EOPD,PRKN-EOPD is characterized by symmetrical,more severe dopaminergic dysfunction and relative increased glucose metabolism.Meanwhile,SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in PRKN-EOPD.

关 键 词：Early-onset Parkinson’s disease PARKIN Dopamine transporter ^(18)F-fluorodeoxyglucose Supplementary motor area 

分 类 号：R742.5[医药卫生—神经病学与精神病学]