Finally, as visualized by 22C11 commercial antibody (Figs 2D and 3D), 12A12mAb immunization resulted to act upstream on Aβ production by normalizing the disease-associated up-regulation in the expression level of APP full-length holoprotein in both Tg Alzheimer’s disease mice models (one-way ANOVA followed by Bonferroni’s post hoc test F(2,18) = 46.07 P < 0.0001 Tg2576; F(2,18) = 97.33 P < 0.0001 3xTg; Tg2576 versus WT ****P < 0.0001; Tg2576 + mAb versus Tg2576 ****P < 0.0001; Tg2576 + mAb versus WT n.s. P = 0.999; ****P < 0.0001 3xTg for all comparisons). Here, APP is linked to early-onset autosomal dominant Alzheimer disease.