Deletion or dominant negative mutations of Trem2 were shown to worsen AD progression in the 5xFAD and APP/PS1 mouse models of AD (Jay et al., 2015, 2017; Yuan et al., 2016; Ulland et al., 2017), but Trem2 deletion also reduced amyloid β burden, increased neuronal loss, prevented microglial association with the plaques, and resulted in their apoptosis in the 5xFAD model (Wang Y. et al., 2015). This evidence concerns the gene PSEN1 and Alzheimer disease.