Among the genes on chromosome 21 triplicated in DS the evidence is compelling that increased gene dose for APP, with increased levels of the APP protein and its products, is necessary for AD-DS (Prasher et al., 1998; Korbel et al., 2009; Wiseman et al., 2015; Ballard et al., 2016; Doran et al., 2017). This evidence concerns the gene APP and Alzheimer disease.