Alpha secretase cuts within the Ab region to produce APPas, an 83-residue COOH-terminal fragment (CT83 or a stub)

(Thesis of Cécile Dumanchin-Notch,  1999, Equipe INSERM EPI 9906 Rouen) 
 

Production of Ab peptide in the different compartments of the cell. Here is presented the alpha secretase cleavage, in the middle of Ab peptide, between amino acids 16 and 17, which is  non amyloidogenic, because it avoids the production of the complete Ab peptide.

Two members of a disintegrin and metalloprotease (ADAM) family, tumor necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE or ADAM-17) and ADAM-10, are candidate alpha-secretases. TACE cleaves pro-TNF-alpha, releasing the extracellular domain (TNF-alpha) in a manner similar to that of APP. TACE apparently processes a spectrum of type 1 membrane glycoproteins, including TNF-alpha, the p75 TNF receptor, L-selectin adhesion molecule, and TGF-alpha.

Another metalloprotease, ADAM-10, also seems to process APP in an alpha-secretase-like manner (Lammich et al., 1999; Lopez-Perez et al., 2001).

Because it is likely that several proteases contribute to alpha-secretase activity, it may be difficult to regulate APP processing pharmacologically through this pathway (Suh and Checler, 2002).