Department of Clinical and Movement Neurosciences, Institute of Neurology, UCL, London, UK.
Institute of Health and Care Research, University of Plymouth Peninsula School of Medicine, Plymouth, UK.
Mov Disord. 2021 Mar;36(3):774-779. doi: 10.1002/mds.28375. Epub 2020 Dec 5.
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 C-(R)-PK11195 binding potentials, and dopamine terminal integrity with F-dopa influx constants.
The C-(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 C-(R)-PK11195 binding potential in the occipital and temporal lobes, cerebellum, hippocampus, and mesencephalon. The degree of hyposmia correlated with nigral C-(R)-PK11195 regional binding potentials (Spearman's rank, P = 0.0066). Mean striatal F-dopa uptake was similar to healthy controls.
In vivo C-(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.
葡萄糖脑苷脂酶基因突变是帕金森病的常见遗传风险因素。它们表现出不完全外显率。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激活和多巴胺完整性。
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激活作为 C-（R）-PK11195 结合势，并用 F-多巴摄取常数测量多巴胺末端完整性。
与对照组相比，葡萄糖脑苷脂酶基因突变携带者的黑质中 C-（R）-PK11195 结合势增加（学生 t 检验；右侧，t=-4.45，P=0.0001）。统计参数映射还定位了在枕叶和颞叶、小脑、海马体和中脑显著增加的 C-（R）-PK11195 结合势。嗅觉减退的程度与黑质 C-（R）-PK11195 区域结合势相关（Spearman 等级，P=0.0066）。纹状体的 F-多巴摄取率与健康对照组相似。
体内 C-（R）-PK11195 PET 成像在无帕金森病的葡萄糖脑苷脂酶基因突变携带者中检测到易患路易体病理的大脑区域的神经炎症。© 2020 作者。运动障碍由 Wiley 期刊公司代表国际帕金森病和运动障碍协会出版。
