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Doo Kim
Author with expertise in Mechanisms of Alzheimer's Disease
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A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer’s disease

Joseph Park et al.Jun 27, 2018
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. This study describes a 3D human neuron-astrocyte-microglia triculture model of Alzheimer’s disease using a microfluidic platform and recapitulating plaque and tangle pathology, microglial recruitment, neuroinflammation, and cell death.
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