A reduction in PICALM levels is well established, which in turn results in a diminished activation of Rab5 and Rab11 for endosomal trafficking.28 Hence, an enrichment of Rab5-positive endosomes may not necessarily result in a greater rate of transcytosis of Aβ as Rab5-mediated endocytosis is defective in Alzheimer’s disease. This evidence concerns the gene PICALM and early-onset autosomal dominant Alzheimer disease.