TREM2 and Alzheimer disease: Some of the most compelling data supporting a critical role of neuroinflammation in AD pathogenesis come from the demonstration that loss-of-function variants in the protein TREM2 confer up to a 4.5 fold increased risk of developing late onset AD (Guerreiro et al., 2013; Jonsson et al., 2013), positioning reduced TREM2 activity as the second strongest known risk factor for AD after APOE ε4 (Liu et al., 2013).