FIGURE 1.

Proteolytic processing of APP. A, the schematic structure of APP is shown with the Aβ domain shaded in red and enlarged. The major sites of cleavage by α-, β-, and γ-secretases are indicated along with Aβ numbering from the N terminus of Aβ (Asp¹). B, non-amyloidogenic processing of APP refers to sequential processing of APP by membrane-bound α- and γ-secretases. α-Secretase cleaves within the Aβ domain, thus precluding generation of intact Aβ peptide. The fates of N-terminally truncated Aβ (p3) and AICD are not fully resolved. C, amyloidogenic processing of APP is carried out by sequential action of membrane-bound β- and γ-secretases. CTF, C-terminal fragment.