Thus, since ApoE primarily binds to LDL-R and LDLR-related protein 1 (LRP1) in the brain, mediating the endocytosis and clearance of ApoE lipoproteins [66], the overexpression of LDL-R is an effective approach to significantly induce ApoE reduction and consequent alleviation of pathologic changes in AD mouse models [67,68,69]. Here, LRP1 is linked to Alzheimer disease.