APP and Alzheimer disease: These mutations in APP and presenilin are closely linked to the Aβ production process, providing a rational basis for the idea that Aβ production and/or Aβ amyloid fibril formation represent the central pathogenic cause of AD (Hardy and Allsop, 1991; Selkoe, 1991; Hardy and Higgins, 1992; Hardy and Selkoe, 2002).