Remarkably, a single intraperitoneal insulin injection improves NOR performance in 3xTg-AD mice fed HFD [279], and similarly intranasal insulin enhances NOR in both ApoE ε3 and ApoE ε4 mice fed HFD, whereas it only improves MWM performance in ApoE ε3 mice [278]. This evidence concerns the gene APOE and Alzheimer disease.