PICALM, the gene encoding phosphatidylinositol binding clathrin assembly protein PICALM [1, 2], is a highly validated genetic risk factor for late onset Alzheimer’s disease (LOAD) [3–23], and one of the most significant susceptibility factors for LOAD after APOE and BIN1 [3, 4, 11, 15, 20]. This evidence concerns the gene PICALM and early-onset autosomal dominant Alzheimer disease.