Processing of APP by secretases. APP (85 kD) can be cleaved by α-secretase (α). This generates soluble APPα (sAPPα; 76 kD) and C-terminal fragment C83 (CTFα; ~9 kD). In the amyloidogenic pathway, APP is cleaved by β-secretase (β) to generate of sAPPβ (74 kD) and the C-terminal fragment C99 (CTFβ; approximately 11 kD), which in turn is cleaved by γ-secretase (γ) to generate amyloid-β (Aβ; approximately 4.5 kD) and amyloid intracellular domain AICD (CTFγ; approximately 6 kD). AICD is also produced when C83 is cleaved by γ-secretase . This cleavage generates also P3 (approximately 2.6 kD). The N-terminal fragment of sAPPβ can be cleaved by an as yet unconfirmed protease as N-APP (approximately 30 kD) and sAPP55 (approximately 45 kD) . Arrowheads indicate caspase-3 cleavage site of APP amino acids (aa) . WO-2 and 22C11 are used in this study as antibodies (ab) to detect the shown fragments. The dotted line pentagons indicate the binding sites of the antibodies.