Figure 1

Generation of different amyloid-beta domain-derived peptides from the amyloid precursor protein. The amyloid precursor protein (APP) is preferentially cleaved in the non-amyloidogenic pathway by α-secretase into a large ectodomain called sAPPα, and into a C-terminal stub called α-C-terminal fragment (α-CTF), which is further processed by γ-secretase into p3 peptides. Alternatively, APP may be cleaved in the amyloidogenic pathway by β-secretase into an ectodomain called sAPPβ and into a longer C-terminal stub called β-C-terminal fragment (β-CTF). This stub is preferentially cleaved by γ-secretase to generate amyloid-beta (Aβ) peptides, but some β-CTF precursors are cleaved by α-secretase resulting in C-terminal truncated Aβ species.