APP and familial Alzheimer disease: Such alteration of the morphology of endosomes is still considered as the earliest neuropathological hallmark of AD since it occurs in the neocortex of patients with sporadic AD, in Familial early onset AD (FAD) with mutations in the gene encoding the Amyloid Precursor Protein (APP), and in DS individuals carrying a trisomy for human chromosome 21 (HSA21) before amyloid peptides deposition [9, 14].