In dominant inherited forms of AD (including mutations in γ-secretase subunits, PSEN1 and PSEN2) the formation of amyloid plaques is promoted by an increased production of Aβ1−42, while in sporadic AD it is mainly due to impaired Aβ clearance (Mawuenyega et al., 2010; Lane et al., 2018). Here, PSEN1 is linked to Alzheimer disease.