Microglia and its Genetics in Alzheimer's Disease
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Updated: Oct 14, 2025
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Xinyan Liang1, Haijian Wu1, Mark Colt1
1Center 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.
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.
Insights
Neuroinflammation, driven by microglia, is key in Alzheimer's Disease (AD) pathogenesis. Understanding microglia
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Alzheimer's Disease (AD) is the leading cause of dementia globally.
- While amyloid-beta (Aβ) and tau proteins were historically central, neuroinflammation is now recognized as a critical factor in AD.
- Microglia, the primary immune cells of the central nervous system (CNS), are central to neuroinflammation in AD.
Purpose of the Study:
- To explore the role of microglia and their associated genetic landscape in Alzheimer's Disease.
- To understand how microglia subtypes and AD risk genes influence disease pathogenesis and progression.
- To provide insights into potential therapeutic targets for AD by analyzing microglia functions.
Main Methods:
- Review of preclinical studies focusing on microglia in AD.
- Analysis of genetic profiles of different microglia subtypes identified in AD.
- Examination of the link between AD risk genes (e.g., APOE, TREM2) and microglial functions.
Main Results:
- Microglia transition from homeostatic to activated states during inflammatory responses in AD.
- Distinct microglia subtypes with specific genetic signatures are associated with AD.
- Many AD risk genes are enriched in microglia, influencing their roles in inflammation and Aβ clearance.
Conclusions:
- Mapping AD risk genes within microglia is crucial for understanding AD etiology.
- Microglia play a significant role in AD pathogenesis through inflammation and Aβ processing.
- Further research into microglia-specific genes may reveal novel therapeutic strategies for Alzheimer's Disease.
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