Interestingly, our recent study (Zhao et al., 2015) indicates that phosphatidylinositol binding clathrin assembly protein (PICALM; Dreyling et al., 1996; Tebar et al., 1999), a highly-validated risk factor for AD confirmed in several genome-wide association studies (Harold et al., 2009; Lambert et al., 2009; Carrasquillo et al., 2010, 2015; Chen et al., 2012; Tanzi, 2012; Liu et al., 2013; Morgen et al., 2014) binds to the intracellular tail of LRP1 at the YXXL domain and regulates endocytsosis of LRP1-Aβ complexes. Here, PICALM is linked to Alzheimer disease.