APOE and Cognitive impairment: Animal model studies revealed that brain levels of VEGF and its receptor (VEGFR-2) were reduced in the hippocampus of apoE4-targeted replacement mice compared with the corresponding apoE3 mice and that upregulation of the levels of hippocampal VEGF utilizing a viral vector reversed the apoE4-driven accumulation of Aβ and hyperphosphorylated tau in hippocampal neurons and the associated synaptic and cognitive impairments [69].