The relevance of Aβ-LRP1 trafficking in Alzheimer’s disease pathogenesis is accentuated by the identification of several endocytic-related genes that amplify the risk of late-onset Alzheimer’s disease, including PICALM, BIN1 and RIN3,30–32 and abnormalities in the vesicular endosomal system.33–39 Hence, dysfunctions in the endocytic pathways appear to contribute to Alzheimer’s disease pathology. Here, PICALM is linked to early-onset autosomal dominant Alzheimer disease.