The importance of TREM2 was also demonstrated in the 5xFAD mouse model of AD, where TREM2 overexpression reduced the hippocampal neuroinflammation, while TREM2 deficiency induced forkhead box protein O3 (FoxO3a) activation and deactivated phosphoinositide 3-kinases/protein kinase B (PI3K/PKB) signaling pathway, thus, increased neuroinflammation [134]. Here, FOXO3 is linked to Alzheimer disease.