The evidence supporting the protective role is that TREM2 knockout (KO) or TREM2 R47H variant dramatically enhanced tau seeding and spreading around plaques in AD mice.175–177 But other studies found that TREM2 deficiency significantly reduced brain atrophy and prevented microglial activation in tau transgenic mice.178,179 Notably, the impact of TREM2 on Aβ and tau pathology may vary at different disease stages. This evidence concerns the gene MAPT and Alzheimer disease.