AD-associated mutations in PS (PS1), a constituent protein of the γ-secretase complex, reduce γ-secretase activity, leading to decreased production of Aβ, especially Aβ40 (Chen et al., 2002; Walker et al., 2005; Bentahir et al., 2006; Shen and Kelleher, 2007; Xia et al., 2015). The gene discussed is PSEN1; the disease is Alzheimer disease.