APP and Alzheimer disease: Using an APP/PS1 AD mouse model, Jay et al. found that TREM2 deficiency reduced Aβ deposition in the young APP/PS1 mice, but exacerbated amyloidopathy in old APP/PS1 mice.228 Using the same model, TREM2 deficiency was also found to eliminate macrophages, attenuating inflammation and amyloid/tau pathologies.229 In distinct tau mouse models, TREM2 deletion have yielded more diverse results.230–233 It seems that the role of TREM2 in AD is dosage- and time-dependent.