• Neuroscience · May 2023

    Review

    Molecular insights into cell type-specific roles in alzheimer's disease: human induced pluripotent stem cell-based disease modeling.

    • Wenhui Qu, Peter Canoll, and Gunnar Hargus.
    • Department of Pathology and Cell Biology, Columbia University, New York, NY, United States; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States.
    • Neuroscience. 2023 May 10; 518: 102610-26.

    AbstractAlzheimer's disease (AD) is the most common cause of dementia resulting in widespread degeneration of the central nervous system with severe cognitive impairment. Despite the devastating toll of AD, the incomplete understanding of the complex molecular mechanisms hinders the expeditious development of effective cures. Emerging evidence from animal studies has shown that different brain cell types play distinct roles in the pathogenesis of AD. Glutamatergic neurons are preferentially affected in AD and pronounced gliosis contributes to the progression of AD in both a cell-autonomous and a non-cell-autonomous manner. Much has been discovered through genetically modified animal models, yet frequently failed translational attempts to clinical applications call for better disease models. Emerging evidence supports the significance of human-induced pluripotent stem cell (iPSC) derived brain cells in modeling disease development and progression, opening new avenues for the discovery of molecular mechanisms. This review summarizes the function of different cell types in the pathogenesis of AD, such as neurons, microglia, and astrocytes, and recognizes the potential of utilizing the rapidly growing iPSC technology in modeling AD.Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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