In addition, the induction of insulin-resistant brain state following ICV-STZ further exacerbates the biochemical, immunohistochemical and behavioral hallmarks in two different models of hereditary AD, such as Tg2576 (APPKM670/671NL Swedish mutation) [35] and 3xTg (APP Swedish, MAPT P301L, and PSEN1 M146V) [36] mice. This evidence concerns the gene APP and Alzheimer disease.