PSEN1 and Alzheimer disease: Familial AD mutations in the APP and PSEN1 genes affect the proteolytic processing of the amyloid precursor protein (APP), with increased accumulation of Aβ peptides (especially Aβ42) causing neuronal toxicity (Hardy and Selkoe, 2002; Haass and Selkoe, 2007; Reiss et al., 2018).