APP and Alzheimer disease: Mutations in the human APP gene (Goate et al., 1991) or the genes coding for presenilin 1 or 2, catalytic subunits of γ-secretases (Rogaev et al., 1995; Sherrington et al., 1995), which cause an increase in Aβ levels or shift the balance of Aβ peptides of different lengths in favor of the production of Aβ1-42, remain the only known causes for early-onset familial manifestations of AD.