Restricting our survey of the literature to data from Alzheimer's disease (AD) mouse models, it is apparent that the multiplicity of genomic manipulations aimed at overexpressing the three main human mutated proteins (APP, Tau, and presenilin (1) separately or jointly in likewise multiple wild-type (Wt) genetic backgrounds did not entirely reproduce, or even failed to model, the symptoms of human pathology. This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.