Familial Alzheimer’s disease-associated PS1 mutations are thought to promote AD by modulating γ-secretase activity, particularly on APP, producing a higher ratio of Aβ42/40 and a lower AICD level (Walker et al., 2005; Wiley et al., 2005; Bentahir et al., 2006; Kumar-Singh et al., 2006). The gene discussed is PSEN1; the disease is Alzheimer disease.