Considering the similar phenotype characterizing AD patients carrying PS1 or PS2 mutations, as well as SAD patients, and the similar increased Aβ deposition in mouse models expressing either FAD-PS1 or FAD-PS2 (usually in combination with human FAD-APP), it is tempting to speculate that if the loss-of-function pathogenic hypothesis is correct for FAD-PS1 models, it should be also valid for FAD-PS2-linked forms. The gene discussed is APP; the disease is Alzheimer disease.