PSEN1 and Alzheimer disease: Mutations in APP, PS1, and PS2 result in the aberrant cleavage of APP into Aβ peptides of 40 residues (Aβ40) or of 42 residues (Aβ42), which are thought to form toxic Aβ plaques responsible for causing neuronal cell death in AD (Hardy and Higgins, 1992).