Sayed et al. [292] found that, in the Tau-P301S (PS19) transgenic mouse model, TREM2 knockout was protective against tau-mediated microglial reactivity and atrophy but that TREM2 haplo-insufficiency or the AD-associated TREM2-R47H variant led to elevated expression of proinflammatory markers, exacerbated atrophy, and increased tau pathology [279]. This evidence concerns the gene TREM2 and Alzheimer disease.