APOE and Alzheimer disease: Several lines of evidence point to the fact that apoE4 is highly susceptible to proteolysis compared to apoE3, and that the link between apoE4 and AD may be in generation of stable fragments that enhance pathology.ApoE (≈34 kDa) contains two domains, referred to as the N-terminal (≈ 22 kDa) and C-terminal (≈10 kDa) domains, which are connected by a short hinge region [3].