First, the 3xTg-AD mouse carries familial mutations of AD from conception as transgenes in amyloid precursor protein (APP; KM670/671NL) and microtubule-associated protein tau (MAPT; P301L) in combination with a knock-in mutation of presenilin 1 (PSEN1; M164V; Oddo et al., 2003; Javonillo et al., 2022). Here, PSEN1 is linked to Alzheimer disease.