Molecular Mechanisms of the Central Regulator of TREM2 Dysfunction

The goal of this project is to apply a novel, systems biology approach that leverages multi-omics in stem cells and human tissues to elucidate the mechanisms by which common genetic drivers of neuroinflammation confer resilience to neurodegenerative disease. Rare variants in the gene TREM2 are associated with a significantly increased risk of Alzheimer’s, Parkinson’s, and frontotemporal lobar degeneration. Our proposal focuses on the gene MS4A4A, which we have identified as a new regulator of TREM2 that may contribute to AD resilience. If successful, the project could lead to a deeper mechanistic understanding of the pathological mechanisms by which TREM2, MS4A4A contribute to disease and to the identification of candidate biomarkers and therapeutic targets.