Our results indicate that the local anti-amyloidogenic action exerted in vivo, both in the hippocampus and retina from symptomatic Tg2576 AD mouse model, by the cleavage-specific tau 12A12mAb entails a concomitant modulation in: (i) two key adaptors of the clathrin-mediated endocytic pathway (BIN1, RIN3) which control the BACE1-triggered APP maturation along the β/γ-mediated amyloidogenic route; (ii) the metabolic utilization of glucose along the glycolytic route (i.e., L-lactate production) and the mitochondrial oxidative phosphorylation pathway. The gene discussed is APP; the disease is Alzheimer disease.