Personalised medicine approach for novel microglia-associated genetic variants in Alzheimer’s disease

The role of inflammation and innate immune system in Alzheimer’s disease (AD) has been recently emphasized as GWAS and WES studies as well as functional studies have identified several AD-associated genes, including TREM2, ABI3, and PLCG2 that are expressed selectively or preferentially in microglia in the brain. These genetic and functional findings highlight an essential role for the innate immune system in the onset and progression of AD and thus provide also novel biomarker and therapeutic prospects for precision medicine applications. The goal in the PMG-AD project is to establish a personalized medicine-based approach for identification of early biomarkers and therapeutic targets in AD by focusing on novel AD-associated genetic variants in ABI3 (S209F; risk variant) and PLCG2 (P522R; protective variant) genes. ABI3 and PLCG2 are preferentially expressed in microglia, reinforcing the idea that microglia-mediated innate immune response directly contributes to the development of AD. Thus, the rationale in PMG-AD is that the protein-altering changes in ABI3 and PLCG2 represent the extreme ends in the genotype-phenotype spectrum with respect to microglia functions in AD.