In the following, we will systematically discuss (1) the correlations between sTREM2 dynamics and AD-related neuropathological hallmarks; (2) the interplay between sTREM2 expression and AD-risk genetic modifiers; and (3) effects of sTREM2 on Aβ accumulation, tau hyperphosphorylation, and synaptic dysfunction. This evidence concerns the gene MAPT and Alzheimer disease.