From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders (N.P.R.), Department of Neurology, McGovern Medical School, The University of Texas Health Science Center, Houston; Department of Neurology (O.C., L.F.), The University of Texas at Austin; School of Medicine (L.B.L.), University of Washington, Seattle; Neuropsychiatry Program (G.D.C., A.L.T.), Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas, Houston; Houston Methodist Research Institute and Weill Cornell Medicine (P.Z.-F., M.Y.), TX; and HDSA Center of Excellence at University of Texas Health Science Center at Houston (E.F.S.).
Neurol Neuroimmunol Neuroinflamm. 2021 Apr 1;8(3). doi: 10.1212/NXI.0000000000000984. Print 2021 May.
To define the role played by microglia in different stages of Huntington disease (HD), we used the TSPO radioligand [11C]-ER176 and PET to evaluate microglial activation in relation to neurodegeneration and in relation to the clinical features seen at premanifest and manifest stages of the disease.
This is a cross-sectional study in which 18 subjects (6 controls, 6 premanifest, and 6 manifest HD gene carriers) underwent a [11C]-ER176 PET scan and an MRI for anatomic localization. Segmentation of regions of interest (ROIs) was performed, and group differences in [11C]-ER176 binding (used to evaluate the extent of microglial activation) were assessed by the standardized uptake value ratio (SUVR). Microglial activation was correlated with ROIs volumes, disease burden, and the scores obtained in the clinical scales. As an exploratory aim, we evaluated the dynamic functions of microglia in vitro, by using induced microglia-like (iMG) cells from peripheral blood monocytes.
Individuals with manifest HD present higher [11C]-ER176 SUVR in both globi pallidi and putamina in comparison with controls. No differences were observed when we compared premanifest HD with controls or with manifest HD. We also found a significant correlation between increased microglial activation and cumulative disease burden, and with reduced volumes. iMG from controls, premanifest HD, and manifest HD patients showed similar phagocytic capacity.
Altogether, our data demonstrate that microglial activation is involved in HD pathophysiology and is associated with disease progression.
为了明确小胶质细胞在亨廷顿病（HD）不同阶段所起的作用，我们使用 TSPO 放射性配体 [11C]-ER176 和 PET 评估了与神经退行性变相关的小胶质细胞激活，以及与疾病前显型和显型阶段所见临床特征相关的小胶质细胞激活。
这是一项横断面研究，共纳入 18 名受试者（6 名对照组、6 名前显型和 6 名显型 HD 基因突变携带者），进行了 [11C]-ER176 PET 扫描和 MRI 解剖定位。进行了感兴趣区（ROI）的分割，通过标准化摄取值比（SUVr）评估 [11C]-ER176 结合（用于评估小胶质细胞激活程度）的组间差异。小胶质细胞激活与 ROI 体积、疾病负担以及临床量表评分进行了相关性分析。作为探索性目的，我们使用外周血单核细胞诱导的小胶质细胞样（iMG）细胞，评估了小胶质细胞在体外的动态功能。
与对照组相比，显型 HD 个体的双侧苍白球和壳核的 [11C]-ER176 SUVr 更高。在与对照组或显型 HD 比较时，前显型 HD 组未观察到差异。我们还发现，小胶质细胞激活增加与累积疾病负担以及体积减少呈显著相关。来自对照组、前显型 HD 和显型 HD 患者的 iMG 显示出相似的吞噬能力。
总之，我们的数据表明，小胶质细胞激活参与了 HD 的病理生理学过程，并与疾病进展相关。
