Sequential regulated proteolysis of APP by different secretases (Lichtenthaler et al., 2011; Haass et al., 2012) results in multiple break-down products including soluble ectodomains, the Aβ-peptides forming the amyloids in Alzheimer’s disease, and the APP intracellular domain (AICD) that is released into the cytosol (Selkoe and Hardy, 2016). Here, APP is linked to early-onset autosomal dominant Alzheimer disease.