In this study, hyperglycemia increased BACE1 expression, Aβ deposition, tau protein phosphorylation, gliosis, and peripheral inflammation and decreased the levels of activated Akt and pS9-GSK3β (the inactive form of GSK3β) in 3×Tg-AD mice, whereas the AM404 treatment reversed these changes. The gene discussed is GSK3B; the disease is Alzheimer disease.