In some rare cases, early-onset familial forms of AD (EOFAD, occurring before 65 years of age) arise due to dominant mutations in one of four genes: presenilin 1 (PSEN1), presenilin 2 (PSEN2), amyloid β precursor protein (APP) and sortilin-related receptor 1 (SORL1) (reviewed by Barthelson et al., 2020a; Bertram and Tanzi, 2012; Ayodele et al., 2021). Here, PSEN1 is linked to Alzheimer disease.