Fig. 4

Proteolytic processing of APP. There are two distinct hydrolysis pathways in APP processing: amyloidogenic pathway (right) and non-amyloidogenic pathway (left). Sequential cleavage of APP by α-secretase and γ-secretase produces a soluble N-terminal peptide (sAPPα), a C-terminal APP intracellular domain (AICD) and a short fragment p3. This is the major secretory pathway with no Aβ production. On the other hand, cleavage by β-secretase and γ-secretase generates sAPPβ, AICD and Aβ [168, 169]. The cleavage sites of secretases are noted. The alternative cleavage of γ-secretase results in two Aβ species: Aβ₄₀ and Aβ₄₂