In DS, which leads to early onset AD, the elevated levels of the β-site cleaved carboxyl-terminal fragment (βCTF) of the amyloid-β precursor protein (APP) that result from the triplication and overexpression of the APP gene are sufficient to cause early endosomal changes (Cataldo et al., 2003; Salehi et al., 2006; Jiang et al., 2010, 2016; Nixon, 2017). This evidence concerns the gene APP and Alzheimer disease.