神经科学
小胶质细胞
神经炎症
神经退行性变
β淀粉样蛋白
人脑
生物
阿尔茨海默病
淀粉样蛋白(真菌学)
疾病
医学
炎症
病理
免疫学
植物
作者
Joseph Park,Isaac Wetzel,Ian Marriott,Didier Dréau,Carla D’Avanzo,Doo Yeon Kim,Rudolph E. Tanzi,Hansang Cho
标识
DOI:10.1038/s41593-018-0175-4
摘要
Alzheimer's disease (AD) is characterized by beta-amyloid accumulation, phosphorylated tau formation, hyperactivation of glial cells, and neuronal loss. The mechanisms of AD pathogenesis, however, remain poorly understood, partially due to the lack of relevant models that can comprehensively recapitulate multistage intercellular interactions in human AD brains. Here we present a new three-dimensional (3D) human AD triculture model using neurons, astrocytes, and microglia in a 3D microfluidic platform. Our model provided key representative AD features: beta-amyloid aggregation, phosphorylated tau accumulation, and neuroinflammatory activity. In particular, the model mirrored microglial recruitment, neurotoxic activities such as axonal cleavage, and NO release damaging AD neurons and astrocytes. Our model will serve to facilitate the development of more precise human brain models for basic mechanistic studies in neural-glial interactions and drug discovery.
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