APP and Alzheimer disease: The amyloid-β cascade hypothesis was based mostly on in vitroand in vivo studies and was further strengthened by theidentification of genetic mutations associated with early-onset AD (e.g. mutation inthe APP gene, and presenilin 1 and 2 genes), and the development of geneticallymodified animal models expressing mutant DNA.5 These mutations lead to a massive overproduction ofAβ and subsequent aggregation into oligomers, and deposition in plaques.