Question

1. Cleavage of APP at which of the following proteolytic cleavage sites produces A-beta40 and A-beta42 (choose all options that apply)
   1. Delta
   2. Alpha
   3. Beta
   4. Gamma

Answer 1

APP or amyloid precursor protein is a transmembrane protein. There are sites for multiple proteolytic cleavage. There are two pathways for cleavage of APP.

a. amyloidogenic pathway and b. non amyloidogenic pathway.

a. for amyloidogenic pathway beta-secretase cuts APP at beta site followed by gamma-secretase cleavage and for this beta-gamma cleavage . Abeta 40 or Abeta 42 is generated.

b. for non amyloidogenic pathway alpha secretase cuts at alpha site followed by gamma secretase . Since alpha secretase cuts in between the Abeta sequences, this cut does not produce any Abeta.

Correct options are C and D (beta and gamma)