Here, we show that: (i) tau protein cleavage at the N-terminal extremity is closely associated with other characteristic neuropathological features of AD into retinas and vitreous bodies of Tg2576 animal model; (ii) these ocular changes—which resemble similar modifications occurring in their brain (i.e. APP/Aβ processing, tau hyperphosphorylation, gliosis, loss of synaptic proteins, microtubule breakdown, mitochondrial energetic deficits, neuronal death)—positively respond to systemic treatment with 12A12mAb. This evidence concerns the gene APP and Alzheimer disease.