An immuno-histochemical study found that apoE expression positively correlates with VEGF and endothelial nitric oxide synthase (eNOS) expression in the capillaries of AD brains.50 Because VEGF suppresses CLDN5 and OCLN expression51 and eNOS increases BBB permeability,52 it is possible that apoE compromises endothelial integrity by modulating those factors. This evidence concerns the gene APOE and Alzheimer disease.