APP and Down syndrome: Studies have detected abnormally enlarged early endosomes and elevated expression of the small guanosine triphosphatase (GTPase), Ras-related proteins RAB5 (early endosome marker), and RAB7 (late endosome marker) in hippocampal neurons in individuals with mild cognitive impairment or AD, as well as in post mortem brain samples from Downs syndrome with AD and the Dp16 mouse model of Downs syndrome (with 3 copies of the amyloid precursor protein gene (App)), and in human-induced pluripotent stem-cell-derived neurons engineered to carry familial AD-associated mutations [4,5,6].