In AD mouse models, significantly lower levels of hippocampal VEGF and its receptor (VEGFR-2) have been reported in ApoE4 carriers compared to ApoE3 carriers, resulting in higher Aβ deposition, p-tau aggregates, synaptic and cognitive impairment, which were then resolved by overexpressing VEGF[196, 206]. This evidence concerns the gene APOE and Alzheimer disease.