Here, we found that ICV-STZ remarkably induced AD-like pathological changes, including impaired learning and memory capacities; loss of dendritic and synaptic plasticity; tau hyperphosphorylation; increase in Aβ40/42 and increase in both GSK-3β and BACE1 activities in the male but not female STZ treated rats. Here, GSK3B is linked to Alzheimer disease.