Neuropathological features of Alzheimer’s disease include amyloid plaques, neurofibrillary tangles and Lewy bodies, with the former preceding the latter two. However, it is not fully understood how these compound proteinopathies are interconnected. Here, we show that transplantation of amyloid-β oligomer-activated microglia into the striatum of naïve mice was sufficient to generate all the features of Alzheimer’s disease, including widespread tauopathy and synucleinopathy, gliosis, neuroinflammation, synapse loss, neuronal death, and cognitive and motor deficits. These pathological features were eliminated by microglia depletion and anti-inflammatory drug administration. Our results suggest the crucial roles of microglia-driven inflammation in development of mixed pathology. This study provides not only mechanistic insights into amyloid-β oligomer-triggered proteinopathies but also a novel animal model recapitulating the salient features of Alzheimer’s disease.

中文翻译：

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淀粉样蛋白β激活的小胶质细胞可诱导复合蛋白病


阿尔茨海默病的神经病理学特征包括淀粉样斑块、神经原纤维缠结和路易体，前者先于后两者。然而，目前尚不完全了解这些复合蛋白病是如何相互关联的。在这里，我们表明将淀粉样蛋白β寡聚体激活的小胶质细胞移植到幼稚小鼠的纹状体中足以产生阿尔茨海默病的所有特征，包括广泛的 tau 蛋白病和突触核蛋白病、神经胶质增生、神经炎症、突触丢失、神经元死亡以及认知和运动缺陷。这些病理特征被小胶质细胞耗竭和抗炎药给药消除。我们的结果表明小胶质细胞驱动的炎症在混合病理学的发展中起着关键作用。这项研究不仅提供了对淀粉样蛋白β寡聚体触发的蛋白质病的机制见解，还提供了一种新的动物模型，概括了阿尔茨海默病的显着特征。