Taken together, these data demonstrate that pathological N-terminal truncation of tau with generation of the toxic 20–22 kDa tau fragment occurring in the eyes of Tg2576 AD is linked to the other two well-established pathognomonic features (AT8 site-specific tau hyperphosphorylation and APP/Aβ amyloidogenic processing) detected in their ocular structures (retina and vitreous body) and in a 12A12mAb-reversible manner, as we previously reported to occur in animals’ hippocampi [57]. Here, APP is linked to Alzheimer disease.