The PS2 D439A mutation was first reported in 2001 in an early-onset AD patient with a missense mutation in exon 12 C.439 A > C of the PS2 gene, resulting in the substitution of the aspartic acid encoded by the 439 codon at the C-terminus of PS2 with alanine [15]. This evidence concerns the gene PSEN2 and Alzheimer disease.