APP and Alzheimer disease: Early-onset AD is associated with mutations in the amyloid precursor protein (APP) gene, the presenilin 1 (PS1), and the presenilin 2 gene, which increases the production of the 42aa isoform of amyloid-β, an isoform more closely associated with the development of amyloid plaques than the shorter isoforms (Goate et al., 1991; Borchelt et al., 1996; Duff et al., 1996; Citron et al., 1997; Steiner et al., 1999).