Our major findings are: 1) that STZ-induced persistent hyperglycemia is associated with cognitive dysfunction, 2) that the up-regulated mTOR/S6K signalling causes the formation of tau hyperphosphorylation in hippocampal neurons, 3) that decreased Cav-1 expression contributes to the formation of tau hyperphosphorylation in HGC, and 4) that mTOR/S6K signalling is required for Cav-1-regulated tau hyperphosphorylation. Here, MTOR is linked to Hyperglycemia.