PSEN2 and Alzheimer disease: Further, Aβ plaques are not sufficient to cause AD, however there is a strong association between their formation and the eventual development of AD as demonstrated by rare mutations (including APP, PSEN1, and PSEN2) in familial early- and late-onset AD (Cruchaga et al., 2012; Sassi et al., 2014; Lanoiselée et al., 2017).