TREM2 and Alzheimer disease: The most common TREM2 variant, R47H, was shown to increase the risk of AD by twofold to threefold, and additional TREM2 variants, such as R62H, T66M, H157Y, D87N, also increase the risk of LOAD by affecting TREM2 expression, surface trafficking, shedding, ligand binding or signaling [136–140].