Title:Microglia and its Genetics in Alzheimer's Disease
Volume: 18
Issue: 9
关键词:
阿尔茨海默病，小胶质细胞，神经炎症，AD风险基因，APOE, GWAS。
摘要: 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.
