That accelerated nucleation is a common cause of fAD is also supported by the effects of mutations in APP outside of Aß and by the effects of mutations in PSEN1 and PSEN2. These mutations destabilise enzyme-substrate complexes, increasing the production of the longer Aß peptides that more effectively nucleates amyloid formation (Szaruga et al., 2017; Veugelen et al., 2016). Here, PSEN1 is linked to familial Alzheimer disease.