TREM2 and Alzheimer disease: TREM2 R47H variant has been identified as a risk factor for AD as early as 2013 (Guerreiro et al., 2013), while mechanism studies have implicated that the unwanted mutations in TREM2 can lead to the reduced protective sTREM2 release, diminished microglial viability, and subsequent increased Aβ burden and neuroinflammation (Carmona et al., 2018; Zhao et al., 2018).