APP and Alzheimer disease: In 2009, we described a genetic variant of the amyloid-β protein consisting of an alanine-to-valine substitution at codon 673 of the APP gene, corresponding to the second residue of Aβ sequence (AβA2V), that causes early-onset AD only in the homozygous state, while heterozygous carriers are unaffected even in advanced age [12].