Brain Microglial Activation Increased in Glucocerebrosidase (GBA) Mutation Carriers without Parkinson's disease.
Brain Microglial Activation Increased in Glucocerebrosidase (GBA) Mutation Carriers without Parkinson's disease.
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无帕金森病的葡萄糖脑苷脂酶（GBA）突变携带者的脑小胶质细胞活化增加。
DOI：
10.1002/mds.28375
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Schapira AHV
中科院分区：
文献类型：
--
作者：
Mullin S;Stokholm MG;Hughes D;Mehta A;Parbo P;Hinz R;Pavese N;Brooks DJ;Schapira AHV
葡萄糖脑苷脂酶基因突变是帕金森病的常见遗传危险因素。他们表现出不完全的催眠状态。本研究的目的是测量无帕金森病的葡萄糖脑苷脂酶基因突变携带者与对照组相比的小胶质细胞活化和多巴胺完整性。我们对9名无帕金森病的葡萄糖脑苷脂酶基因突变携带者和29名年龄匹配的对照者进行了PET扫描。我们测量了小胶质细胞的活化作为11 C-（R）-PK 11195结合电位，以及多巴胺末端完整性与18F-多巴内流常数。与对照组相比，葡萄糖脑苷脂酶基因携带者黑质中的11 C-（R）-PK 11195结合潜力增加（Student t检验;右，t = −4.45，P = 0.0001）。统计参数图还定位了枕叶和颞叶、小脑、海马和中脑中显著增加的11 C-（R）-PK 11195结合潜力。嗅觉减退程度与黑质11 C-（R）-PK 11195区域结合电位相关（斯皮尔曼等级，P = 0.0066）。平均纹状体18F-dopa摄取与健康对照相似。体内11 C-（R）-PK 11195 PET成像检测无帕金森病的葡萄糖脑苷脂酶基因突变携带者中易受Lewy病理影响的脑区域的神经炎症。版权所有2020作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版
Glucocerebrosidase gene mutations are a common genetic risk factor for Parkinson's disease. They exhibit incomplete penetrance. The objective of the present study was to measure microglial activation and dopamine integrity in glucocerebrosidase gene mutation carriers without Parkinson's disease compared to controls. We performed PET scans on 9 glucocerebrosidase gene mutation carriers without Parkinson's disease and 29 age‐matched controls. We measured microglial activation as 11C‐(R)‐PK11195 binding potentials, and dopamine terminal integrity with 18F‐dopa influx constants. The 11C‐(R)‐PK11195 binding potential was increased in the substantia nigra of glucocerebrosidase gene carriers compared with controls (Student t test; right, t = −4.45, P = 0.0001). Statistical parametric mapping also localized significantly increased 11C‐(R)‐PK11195 binding potential in the occipital and temporal lobes, cerebellum, hippocampus, and mesencephalon. The degree of hyposmia correlated with nigral 11C‐(R)‐PK11195 regional binding potentials (Spearman's rank, P = 0.0066). Mean striatal 18F‐dopa uptake was similar to healthy controls. In vivo 11C‐(R)‐PK11195 PET imaging detects neuroinflammation in brain regions susceptible to Lewy pathology in glucocerebrosidase gene mutation carriers without Parkinson's. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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