APOE and neurodegenerative disease: In fact, recent microglial transcriptional analyses demonstrated that the TREM2–APOE pathway induces dysregulation of Cx3cr1 and homeostatic signature genes such as P2ry12, Siglech, and Tmem119 in a mouse model of neurodegenerative disease, suggesting that microglia are activated in a detrimental manner in neurodegenerative diseases [14].