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Nat Neurosci. 2018 Jul;21(7):941-951. doi: 10.1038/s41593-018-0175-4. Epub 2018 Jun 27.

A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer's disease.

Park J1,2,3,4,5, Wetzel I1,2,3,4, Marriott I2,3, Dréau D2,3, D'Avanzo C5, Kim DY5, Tanzi RE5, Cho H6,7,8,9.

Author information

1
Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC, USA.
2
Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC, USA.
3
Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA.
4
The Nanoscale Science Program, University of North Carolina at Charlotte, Charlotte, NC, USA.
5
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
6
Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC, USA. h.cho@uncc.edu.
7
Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC, USA. h.cho@uncc.edu.
8
Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA. h.cho@uncc.edu.
9
The Nanoscale Science Program, University of North Carolina at Charlotte, Charlotte, NC, USA. h.cho@uncc.edu.

Abstract

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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PMID:
29950669
DOI:
10.1038/s41593-018-0175-4
[Indexed for MEDLINE]

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