APP and Alzheimer disease: Generation of Aβ peptides and Aβ plaques is believed to have a causal role in the development of AD, as (i) duplications of the APP gene locus (7, 8), (ii) mutations in the C99-encoding region of APP, and (iii) mutations in the C99-cleaving γ-secretase (9, 10) can cause familial AD (FAD).