Figure 1.

A schematic diagram of APP. The amyloid β peptide (Aβ) region contains part of the transmembrane domain (black box) and part of the extracellular domain of APP (green box). Cleavage by β-secretase generates the N terminus, and intramembranous cleavage by γ-secretase gives rise to the C terminus of Aβ. Cleavage by α-secretase precludes Aβ formation. Eleven missense mutations in the transmembrane region of APP are shown, together with the suggested cleavage sites for ε- and ξ-secretases. Red letters indicate mutations tested here.