Table_1_Alterations of Striatal Subregions in a Prion Protein Gene V180I Mutation Carrier Presented as Frontotemporal Dementia With Parkinsonism.docx

ObjectiveTo explore the roles of striatal subdivisions in the pathogenesis of frontotemporal dementia with parkinsonism (FTDP) in a patient resulting from prion protein gene (PRNP) mutation.MethodsThis patient received clinical interviews and underwent neuropsychological assessments, genetic testing, [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET)/MRI, and [18F]-dihydrotetrabenazine positron emission tomography ([18F]-DTBZ PET)/CT. Region-of-interest analysis was conducted concerning metabolism, and dopamine transport function between this patient and 12 controls, focusing on the striatum subregions according to the Oxford-GSK-Imanova Striatal Connectivity Atlas.ResultsA 64-year-old man initially presented with symptoms of motor dysfunction and subsequently behavioral and personality changes. FTDP was initially suspected. Sequence analysis disclosed a valine to isoleucine at codon 180 in PRNP. Compared to controls, this patient had a severe reduction (> 2SD) of standard uptake value ratio (SUVR) in the limbic and executive subregions but relative retention of metabolism in rostral motor and caudal motor subregions using [18F]-FDG PET/MRI, and the SUVR decreased significantly across the striatal in [18F]-DTBZ PET/CT, especially in the rostral motor and caudal motor subregions.ConclusionThe alteration of frontal striatal loops may be involved in cognitive impairment in FTDP, and the development of parkinsonism in FTDP may be primarily due to the involvement of the presynaptic nigrostriatal loops in PRNP V180I mutation.

本研究旨在探讨纹状体亚区在由朊蛋白基因（PRNP）突变引起的具有帕金森综合征的前额叶痴呆（FTDP）发病机制中的作用。方法：患者接受了临床访谈和神经心理学评估、基因检测、[18F]-氟代脱氧葡萄糖正电子发射断层扫描（[18F]-FDG PET）/MRI以及[18F]-二氢去甲四苯烷正电子发射断层扫描（[18F]-DTBZ PET）/CT检查。对代谢和突触前多巴胺转运功能进行了感兴趣区域分析，并与12名对照者进行比较，重点关注牛津-GSK-Imanova纹状体连通性图谱中的纹状体亚区。结果：一位64岁的男性患者最初出现运动功能障碍症状，随后出现行为和性格改变，初步怀疑为FTDP。序列分析显示PRNP基因第180密码子处缬氨酸突变为异亮氨酸。与对照者相比，患者在使用[18F]-FDG PET/MRI检查中，边缘和执行亚区的标准摄取值比率（SUVR）显著降低（> 2SD），而使用[18F]-DTBZ PET/CT检查时，纹状体各区域的SUVR值显著降低，特别是在前运动和尾侧运动亚区。结论：前额叶纹状体环路的变化可能与FTDP的认知障碍有关，而FTDP中帕金森综合征的发展可能主要是由于PRNP V180I突变涉及的突触前黑质纹状体环路受损。