APOE and Alzheimer disease: Knockout or knockdown of TREM2 in AD animal models has been shown to reduce the microglial barrier around plaques, decrease plaque compaction, lower APOE4 levels in APP mice, and increase the presence of dystrophic neurites surrounding plaques (Jay et al., 2015; Wang et al., 2016; Jay et al., 2017; Parhizkar et al., 2019).