of AD-GWAS genes implicated in interacting with misfolded folded protein, surface receptors, or anti-apoptotic events such as CLU (APOJ) (Yeh et al., 2016). Whereas cells exposed to these two factors responded differentially to fAβ, increasing expression of genes involved in neuronal cell surface motif recognition, or phagocytosis of CNS substrates, including MS4A genes, TREM2, TYROBP, CD33, and ABCA7 (Bradshaw et al., 2013; Fu et al., 2016; Greer et al., 2016)(Figure S6B). These studies further support the notion that CD200-CD200R1 and/or CX3CL1-CX3CR1 axis can prime microglia to respond to neurodegenerative conditions (Prinz and Priller, 2014). Thus, exposure to soluble CNS factors, like CD200 and CX3CL1, may allow for access to microglial-specific transcriptional regulator elements (enhancers and promoters) (Gosselin et al., 2014; Lavin et al., 2014), although future studies are required to fully translate these observations.
