Importantly, in AD mouse model, BBB endothelial cells produce a variety of factors, such as thrombin, vascular endothelial growth factor (VEGF), angiopoietin-2, tumor necrosis factor (TNF), transforming growth factor, interleukin (IL) IL-1, IL-6, IL-8, monocyte chemoattractant protein-1, hypoxia-inducible factor-1, MMPs, and integrins that may promote AD pathogenesis65. Here, TNF is linked to Alzheimer disease.