APP and familial Alzheimer disease: Studies by McPhie et al. (2001) demonstrated that overexpression of the APP-C31 peptide in primary cortical neurons via an HSV vector significantly increased apoptosis over controls, that the generation of APP-C31 occurred in the absence of γ-secretase cleavage, and that this toxic pathway was enhanced in the presence of familial Alzheimer’s disease (FAD) β-site mutations.