Abstract

Genetic studies have identified numerous candidate risk loci linked to Alzheimer’s disease (AD), a disease that primarily affects older adults. Nevertheless, the genetic causes of AD are still not fully understood for most late-onset patients. Recent studies suggest that phagocytosis, the process by which microglia engulf and remove toxic substances in the brain, such as amyloid-beta and Tau proteins, is a pathological hub in AD. Additionally, Non-coding AD variants may contribute to the disease by disrupting the expression of genes involved in phagocytosis.
The goal of this proposed study is to provide a comprehensive annotation of AD-related genes with converging phenotypes in the phagocytosis process and determine how AD-causing variants contribute to AD by modulating the expression of these genes, leveraging our recently developed genomic technologies. Our results will provide deeper insights into the role of microglia in the context of AD. Additionally, it will identify novel therapeutic opportunities by increasing specific phagocytosis efficiencies, ultimately leading to a cure for AD.