A clinically relevant mouse model of the Trem2*R47H Alzheimer’s disease risk variant

The TREM2 (triggering receptor expressed on myeloid cells 2) locus harbors numerous relatively rare variants associated with Alzheimer’s disease risk. The TREM2*R47H allele is one of the strongest genetic risk factors for developing late‐onset Alzheimer’s disease; patients exhibit both earlier onset of symptoms and rapid cognitive decline. TREM2 is expressed by microglia in the brain and plays a key role in modulating microglial activity. TREM2 expression is increased in AD and is associated with recruitment of microglia to amyloid plaques. An experimental model is therefore critical to study mechanisms of late‐onset AD, and the MODEL‐AD set out to create a clinically relevant mouse model.