Fig. 1.

APP processing and APP mutations. Aβ42 is encoded by amino acids 672–713 of APP (numbered according to the longest isoform, APP770). Aβ is produced through sequential cleavage by β-secretase, then γ-secretase. γ-secretase can cleave at alternate sites to produce Aβ40 or Aβ42. Alternative APP processing by α-secretase prevents Aβ production. Common APP mutations include the Swedish mutation at the β-secretase cleavage site and multiple named and unnamed mutations at the γ-secretase cleavage site. Intra-Aβ mutations are also shown.