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). Here, APP is linked to Alzheimer disease.