Increased expression of the APP gene, due either to duplication of the APP locus (APPdup) (Rovelet-Lecrux et al., 2006, Sleegers et al., 2006), or trisomy of chromosome 21 (Rumble et al., 1989)—containing the APP gene—in Down syndrome (trisomy 21 [TS21]), also leads to increased production and accumulation of Aβ peptides and the early onset of AD pathology. This evidence concerns the gene APP and Alzheimer disease.