PSEN2 and Alzheimer disease: Since its identification, APOE ε4 allele has been regarded as a risk factor for SAD instead of FAD, because it is neither necessary nor sufficient to cause AD (Cacace et al. 2016), and its inheritance does not follow an autosomal dominant pattern such as APP, PSEN1, and PSEN2 mutations (van Duijn et al. 1994; Frisoni et al. 2022).