The 900 genomes were initially examined for variants in AD-associated genes (PSEN1, PSEN2, and APP), and the protein altering variants were curated according to the ACMG guidelines for the interpretation of genetic variants [55] and the algorithm proposed by Guerreiro et al. [58] to determine pathogenicity (Additional file 1: Figures S14, S15 and Additional file 7: Supplementary methods). This evidence concerns the gene APP and Alzheimer disease.