Objective: The aim of this cross−sectional single center study was to investigate 18kDa translocator protein (TSPO)−PET as a biomarker for microglial activation in the 4−repeat tauopathies corticobasal degeneration and progressive supranuclear palsy (PSP). Methods: Specific binding of the TSPO tracer 18F−GE−180 was determined by serial PET during pharmacological depletion of microglia in a 4−repeat tau mouse model. TSPO−PET was performed in 30 patients with corticobasal syndrome (CBS, 68±9 years, 16 female) and 14 patients with PSP (69±9 years, 8 female), and 13 control subjects (70±7 years, 7 female). Group comparisons and associations with parameters of disease progression and sTREM2 were assessed by region-based and voxel−wise analyses. Results: Tracer binding was significantly reduced after pharmacological depletion of microglia in 4−repeat tau mice. Elevated TSPO labeling (standardized−uptake−value−ratios) was observed in subcortical brain areas of CBS and PSP patients when compared to controls, most pronounced in the globus pallidus internus (CBS: 1.039 [95%CI 1.000−1.078, p<0.001], PSP: 1.046 [95%CI: 0.990−1.101, p<0.001], controls: 0.861 [95%CI 0.802−0.921]), whereas only CBS patients showed additionally elevated tracer binding in motor and supplemental motor areas. TSPO labeling was only correlated weakly with parameters of disease progression in CBS and PSP but allowed sensitive detection of 4−repeat tauopathy patients. sTREM2 did not differ between patients with CBS and controls. Interpretation: Our data indicate a potential of 18F−GE−180 PET to detect microglial activation in the brain of 4−repeat tauopathy patients, fitting to predilection sites of the phenotype. TSPO-PET may serve as a sensitive early disease stage biomarker in 4−repeat tauopathies.

中文翻译：

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4重复性Tauopathies中神经炎症的体内评估

目的：这项横断面单中心研究的目的是研究18kDa转运蛋白（TSPO）-PET作为4重复性tauopathies皮质基底变性和进行性核上性麻痹（PSP）中小胶质细胞活化的生物标志物。方法：在连续4头tau小鼠模型中，小胶质细胞的药理消耗期间，通过连续PET测定TSPO示踪剂18F-GE-180的特异性结合。TSPO-PET在30例肾上腺皮质综合征（CBS，68±9岁，女性16）和14例PSP（69±9岁，8女性）和13例对照（70±7岁，7女性）中进行。 。通过基于区域和体素的分析评估了疾病进展和sTREM2参数的组比较和关联。结果：在4重复tau小鼠中，小胶质细胞的药理作用消失后，示踪剂结合显着降低。与对照组相比，在CBS和PSP患者的皮层下大脑区域观察到TSPO标记升高（标准化摄取值比率），在内glo部最明显（CBS：1.039 [95％CI 1.000-1.078，p <0.001] ]，PSP：1.046 [95％CI：0.990-1.01，p <0.001]，对照组：0.861 [95％CI 0.802-0.921]），而只有CBS患者在运动和辅助运动区域的示踪剂结合水平更高。TSPO标记仅与CBS和PSP中疾病进展的参数弱相关，但允许灵敏地检测4重复性tauopathy患者。sTREM2在CBS患者和对照组之间没有差异。解释：我们的数据表明18F-GE-180 PET可以检测4重复性tauopathy患者的大脑中的小胶质细胞活化，适合表型的好发部位。TSPO-PET可以作为4重复性疾病的敏感的早期疾病生物标记。