TREM2 and Alzheimer disease: However, subsequent evidence (Krasemann et al., 2017) revealed that TREM‐2 activation by apolipoprotein E (APOE), the major risk factor for AD, identified as a TREM2 ligand (Atagi et al., 2015; Bailey, DeVaux, & Farzan, 2015), drives a neurodegenerative phenotype in microglia, characterized by suppression of major transcription factors of homeostatic microglia (PU.1, MEF2a, SMAD3, and TGF‐β signaling) and overlapping to some extent the classical pro‐inflammatory microglia phenotype, featured by high expression of the pro‐inflammatory miRNA miR‐155 (Butovsky et al., 2012).