PSEN2 and Alzheimer disease: The PSEN2 p.V148I mutation was originally reported in a Spanish patient with late-onset AD (AAO = 71 years) (Lao et al., 1998) but, its pathogenicity has been questioned based on the absence of effect on either Aβ42 levels, Aβ40 levels, or the Aβ42/40 ratio in vitro (Walker et al., 2005).