APP and Alzheimer disease: Furthermore, a genetic variation observed in individuals with small internal duplications within chromosome 21 can result in three APP copies in a rare familial trait known as duplication of APP and can lead to an early-onset AD (Rovelet-Lecrux et al., 2006; Sleegers et al., 2006; Kasuga et al., 2009; Thonberg et al., 2011; Hooli et al., 2012; Swaminathan et al., 2012).