Figure 1

Amyloidogenic processing of the β-amyloid precursor protein (APP) by BACE1 and γ-secretase. Initially, BACE1 cleaves APP on the N-terminal end of the Aβ sequence to yield a large secreted N-terminal fragment (sAPPβ) and a smaller membrane-associated C-terminal stub (C99), which is then cleaved by the γ-secretase complex to yield Aβ and an APP intracellular domain (AICD). Secreted Aβ aggregates in the extracellular environment to form neurotoxic oligomers.