Department of Neurology, University Hospital of Munich, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany.
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.
Mov Disord. 2021 Apr;36(4):883-894. doi: 10.1002/mds.28395. Epub 2020 Nov 27.
Neuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4-repeat tauopathies.
The aim of this cross-sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy.
Specific binding of the 18 kDa translocator protein tracer F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model. The 18 kDa translocator protein PET was performed in 30 patients with corticobasal syndrome (68 ± 9 years, 16 women) and 14 patients with progressive supranuclear palsy (69 ± 9 years, 8 women), and 13 control subjects (70 ± 7 years, 7 women). Group comparisons and associations with parameters of disease progression were assessed by region-based and voxel-wise analyses.
Tracer binding was significantly reduced after pharmacological depletion of microglia in 4-repeat tau mice. Elevated 18 kDa translocator protein labeling was observed in the subcortical brain areas of patients with corticobasal syndrome and progressive supranuclear palsy when compared with controls and was most pronounced in the globus pallidus internus, whereas only patients with corticobasal syndrome showed additionally elevated tracer binding in motor and supplemental motor areas. The 18 kDa translocator protein labeling was not correlated with parameters of disease progression in corticobasal syndrome and progressive supranuclear palsy but allowed sensitive detection in patients with 4-repeat tauopathies by a multiregion classifier.
Our data indicate that F-GE-180 PET detects microglial activation in the brain of patients with 4-repeat tauopathy, fitting to predilection sites of the phenotype. The 18 kDa translocator protein PET has a potential for monitoring neuroinflammation in 4-repeat tauopathies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
神经炎症作为神经退行性疾病（包括 4 重复tau 病）的治疗靶点受到越来越多的关注。
本横断面研究旨在探讨 18kDa 转位蛋白正电子发射断层扫描（PET）作为 4 重复 tau 病皮质基底节变性和进行性核上性麻痹中小胶质细胞激活的生物标志物。
通过 4 重复 tau 小鼠模型中小胶质细胞药理学耗竭期间的连续 PET 确定 18kDa 转位蛋白示踪剂 F-GE-180 的特异性结合。对 30 例皮质基底节综合征患者（68±9 岁，16 名女性）和 14 例进行性核上性麻痹患者（69±9 岁，8 名女性）以及 13 名对照者（70±7 岁，7 名女性）进行了 18kDa 转位蛋白 PET 检查。通过基于区域和体素的分析评估组间比较和与疾病进展参数的相关性。
在 4 重复 tau 小鼠中小胶质细胞药理学耗竭后，示踪剂结合明显减少。与对照组相比，皮质基底节综合征和进行性核上性麻痹患者的皮质下脑区观察到升高的 18kDa 转位蛋白标记，在苍白球 internus 中最为明显，而只有皮质基底节综合征患者在运动和补充运动区显示出另外升高的示踪剂结合。在皮质基底节综合征和进行性核上性麻痹中，18kDa 转位蛋白标记与疾病进展参数无关，但通过多区域分类器可以敏感地检测到 4 重复 tau 病患者。
我们的数据表明，F-GE-180 PET 可检测 4 重复 tau 病患者大脑中的小胶质细胞激活，符合表型的易位部位。18kDa 转位蛋白 PET 具有监测 4 重复 tau 病神经炎症的潜力。© 2020 作者。运动障碍由 Wiley 期刊出版社代表国际帕金森病和运动障碍学会出版。
