APP and Alzheimer disease: For example, phosphatidylinositol-binding clathrin assembly protein (PICALM)-mediated Aβ generation and clearance may influence the accumulation of Aβ fragments in AD brains [24], bridging integrator 1 (BIN1) internalizes Aβ peptides and ApoE via the endosomal-lysosomal pathway [25], and SORL1 directs APP to the endocytic pathways for recycling [22].