Mechanism and role of microglial activation in a transgenic mouse model of Alzheimer's disease.

据报道，小胶质细胞参与了包括阿尔茨海默病在内的人类tau病和包括帕金森氏病在内的α-突触核蛋白病的过程。为了探讨小胶质细胞激活在人牛头病和α-突触核蛋白病转基因小鼠模型中的作用和机制，我们对人牛头病和α-突触核蛋白病的小鼠和转基因小鼠模型进行了病理分析。在TgTauR406W 21807系中，小胶质细胞增生与显著的tau积累相关。APPsw小鼠（Tg2576）在7-8个月大时首次出现过早的、有芯的斑块。抗Aβ n1 (D)抗体和DAPI双免疫荧光染色表明，圆形细胞内的Aβ沉积是细胞核和部分胞浆，位于中心核周围，是神经细胞或小胶质细胞。与神经元、少突胶质细胞和星形胶质细胞不同，α-突触核蛋白阳性包涵体在人α-突触核蛋白病患者的大脑中不存在。在α-突触核蛋白病中，小胶质细胞的激活几乎与α-突触核蛋白阳性包涵的分布平行。在少量激活的小胶质细胞中发现了已知的吞噬相关受体MSR-A，并且在死亡神经元周围观察到被激活的小胶质细胞簇，包括被标记为抗mhc II类和MSR-A的吞噬型小胶质细胞。我们的研究表明，小胶质细胞的激活，包括吞噬作用，在tau病和α-突触核蛋白病中可能是系统特异性的，细胞内tau或α-突触核蛋白聚集对小胶质细胞激活的直接贡献可能不太可能。

It has been reported that there is microglial involvement in the process of human tauopathies, including Alzheimer's disease, and α-synucleinopathies, comprising Parkinson's disease. To investigate the mechanism and role of microglial activation in a transgenic mouse model of human tauopathies and α-synucleinopathies, we performed pathological analyses of brains from human tauopathies and α-synucleinopathies and the transgenic mouse model. In the TgTauR406W 21807 line, microgliosis correlated with prominent tau accumulation. APPsw mice (Tg2576) showed first appearance of premature, cored plaques at 7-8 months old. Double immunofluprescence staining using both the anti-AβN1 (D) antibody and DAPI demonstrated that round cellular Aβ deposits was nucleus and partly cytoplasma of some peripheral cells around central cores, which were neuronal cells or microglial cells. In brains from human α-synucleinopathies, α-synuclein-positive inclusions were absent in microglia, unlike neurons, oligodendroglia and astrocytes. In α-synucleinopathies, microglial activation almost paralleled the distribution of α-synuclein positive inclusion. MSR-A, a known phagocytosis-associated receptor, was found in a small number of activated microglia, and the clusters of activated microglia, including the phagocytic type, labeled with anti-MHC class II and MSR-A were observed around dying neurons. Our study indicated that microglial activation, including phagocytosis, could be system-specific in tauopathoies and α-synucleinopathies, and that direct contribution of intracellular tau or α-synuclein aggregation to microglial activation could be unlikely.