Microglia and its Genetics in Alzheimer's Disease

Title:Microglia and its Genetics in Alzheimer's Disease

Volume: 18 Issue: 9

Author(s): Xinyan Liang , Haijian Wu, Mark Colt , Xinying Guo, Brock Pluimer , Jianxiong Zeng, Shupeng Dong and Zhen Zhao*

Affiliation:

• Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033,United States

Keywords: Alzheimer's Disease, microglia, neuroinflammation, AD risk genes, APOE, GWAS.

Abstract: Alzheimer’s Disease (AD) is the most prevalent form of dementia across the world. While its discovery and pathological manifestations are centered on protein aggregations of amyloid- beta (Aβ) and hyperphosphorylated tau protein, neuroinflammation has emerged in the last decade as a main component of the disease in terms of both pathogenesis and progression. As the main innate immune cell type in the central nervous system (CNS), microglia play a very important role in regulating neuroinflammation, which occurs commonly in neurodegenerative conditions, including AD. Under inflammatory response, microglia undergo morphological changes and status transition from homeostatic to activated forms. Different microglia subtypes displaying distinct genetic profiles have been identified in AD, and these signatures often link to AD risk genes identified from the genome-wide association studies (GWAS), such as APOE and TREM2. Furthermore, many AD risk genes are highly enriched in microglia and specifically influence the functions of microglia in pathogenesis, e.g. releasing inflammatory cytokines and clearing Aβ. Therefore, building up a landscape of these risk genes in microglia, based on current preclinical studies and in the context of their pathogenic or protective effects, would largely help us to understand the complex etiology of AD and provide new insight into the unmet need for effective treatment.

Cite this article as:

Liang Xinyan, Wu Haijian , Colt Mark , Guo Xinying, Pluimer Brock , Zeng Jianxiong, Dong Shupeng and Zhao Zhen *, Microglia and its Genetics in Alzheimer's Disease, Current Alzheimer Research 2021; 18 (9) . https://dx.doi.org/10.2174/1567205018666211105140732