Figure 1.

Schematic representation of amyloid precursor protein (APP), positions of the Aβ sequence, transmembrane domain of APP (Tm), and sites of α-, β- and γ-secretase cleavage.

NH₂ and COOH indicate the N-terminus and C-terminus of the protein. Aβ sequence is enlarged below. The constitutive proteolytic cleavage by α- and γ-secretases leads to the formation of the short p3 peptide and processing by β- and γ-secretases leads to Aβ40 and Aβ42 peptides with a consecutive release of a C-terminal APP intracytoplasmic domain (AICD). Also shown are AD/CAA-causing pathogenic amino acid substitutions within APP (see also Table 2 and visit www.molgen.ua.ac.be/ADMutations for a complete and updated list of these mutations).