TLR4 and Alzheimer disease: Regarding ApoE’s interaction with TLRs, it has been described a deleterious effect of the APOE4 genotype in AD through the TLR4-dependent pathway [269], and apoE3 can inhibit macrophage activation driven by TLR4 [280], TLRs recruit TIR domain-containing adaptor proteins such as MyD88, TRIF, TIRAP/TRAM, or TRAM, leading to activation of different signal transduction pathways, including NF-κB and MAP kinases and hence inducing inflammatory cytokine gene expression [281].