期刊
NATURE NEUROSCIENCE
卷 21, 期 7, 页码 941-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0175-4
关键词
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资金
- NIH/NIA [P01 AG015379, RF1 AG048080, R01 AG014713]
- Pioneering Funding Award - Cure Alzheimer's Fund (CAF)
- BrightFocus Foundation
- Duke Energy Special Initiatives - Charlotte Research Institute
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2015R1A6A3A03019848]
- National Research Foundation of Korea [2015R1A6A3A03019848] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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