TREM2: A Target Enabling Package

Single loss of function mutations in TREM2, a receptor expressed by microglia in the brain, are associated with an increased risk of neurodegeneration, including Alzheimer’s disease and Nasu-Hakola disease.  Therefore, drugs enhancing TREM2 activity represent a potential treatment strategy. We identified 4 TREM2-specific scFv antibody fragments by phage display and solved the crystal structures of two of these in complex with the TREM2 ectodomain. The scFv antibodies altered TREM2 ectodomain shedding and TREM2 downstream signalling, representing promising research tools and therapeutic antibodies.