The present results indicate that the dorsal hippocampus of 3×Tg-AD mice exhibits a pronounced transcriptional downregulation of the canonical insulin signaling pathway, including decreased expression of insulin receptor (IR), IGF-1 receptor (IGF1R), IRS-1, PI3K, AKT2, and GSK-3β mRNAs. This evidence concerns the gene GSK3B and Alzheimer disease.