APP and early-onset autosomal dominant Alzheimer disease: Another major substrate of ADAM10 is the amyloid precursor protein (APP) for which ADAM10 acts as the constitutive alpha-secretase (Postina et al., 2004; Lammich et al., 1999; Kuhn et al., 2010; Jorissen et al., 2010) and thus possesses the ability to prevent the generation of the pathogenic Aβ peptide in Alzheimer’s disease (AD) (Lammich et al., 1999; Kuhn et al., 2010).