5xFAD mice contain three AD familial mutations in humanized APP and two in PSEN1 (Goate et al., 1991; Mullan et al., 1992; Eckman et al., 1997; Citron et al., 1998; Berezovska et al., 2005), and exhibit Aβ plaques, neurodegeneration, and cognitive decline as they age (Oakley et al., 2006; Jawhar et al., 2012; Forner et al., 2021; Oblak et al., 2021). Here, PSEN1 is linked to Alzheimer disease.