TREM2 and Alzheimer disease: Both Apolipoprotein E ε4 (APOE ε4), which is the most significant and highly replicated genetic risk factor for AD (Corder et al., 1993; Saunders et al., 1993; Lambert et al., 2013), and the TREM2 R47H polymorphism, which has the second largest effect size (Guerreiro et al., 2013; Jonsson et al., 2013), affect innate immunity and lipid metabolism (Shi and Holtzman, 2018; Nugent et al., 2020).