PSEN2 and Alzheimer disease: While both PSEN1 and PSEN2 mutations are very rare causes of AD (Campion et al, 1999), their study has provided crucial insights into what constitutes pathological amyloid peptide (Aβ) generation (Szaruga et al, 2017; Veugelen et al, 2016; Kretner et al, 2016; Duff et al, 1996; Scheuner et al, 1996; Wagner et al, 2012), which has direct relevance to the understanding of sporadic AD (SAD), as we will discuss below.