LRP-1 binds to Aβ directly (Deane et al., 2004), but also binds indirectly via its ligands including α2-macroglobulin, receptor-associated protein, and apolipoprotein E (ApoE) (Narita et al., 1997; Bu, 2009; Kanekiyo and Bu, 2009). ApoE is the main chaperone of Aβ in central nervous system (Holtzman et al., 2012; Zolezzi et al., 2014). To date, three isoforms of ApoE have been described (ε2, ε3, and ε4), and the ApoE ε4 variant is considered to be one of the most relevant risk factors for AD and CAA (Premkumar et al., 1996; Zolezzi et al., 2014). ApoE immunoreactivity is common in amyloid plaques, suggesting that ApoE interacts with Aβ directly in AD brains and could strongly influence the rate of Aβ removal (Namba et al., 1991; Holtzman et al., 2012). Several authors have proposed ApoE as therapeutic target for Aβ clearance (Cramer et al., 2012; Zolezzi and Inestrosa, 2014). Cramer et al. reported that bexarotene, a retinoid X receptor agonist, stimulated the ApoE-dependent Aβ clearance through the actions of liver X receptors and peroxisome proliferator-activated nuclear receptor gamma in AD model mice
