The main finding of the present study is that ICV-STZ mice develop AD-relevant N-terminal cleavage of tau, with the generation of toxic peptide(s), such as the 20–22 kDa fragment [38], in tight association with their cognitive impairment (assessed as NOR and OPR performance tasks) and with other key neurochemical (amyloidogenesis, tau hyperphosphorylation, gliosis, synaptic alterations assessed by Western blotting and immunofluorescence) and histological (cell loss/injury evaluated by hematoxylin and eosin staining) hallmarks. The gene discussed is MAPT; the disease is Alzheimer disease.