Subsequent work demonstrated that amyloid beta (Aβ), a small peptide which forms aggregates in the brains of AD patients (Glenner and Wong, 1984), was generated by cleavage of APP by γ-secretase (Haass and Selkoe, 1993; Shoji et al., 1992), of which the catalytic subunit is PSEN1 or PSEN2 (De Strooper et al., 1998; Wolfe et al., 1999). This evidence concerns the gene PSEN1 and Alzheimer disease.