Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

Carter, Chris J.

Theobromine is a phosphodiesterase inhibitor and downregulates PDE4 in a glioma cell line [317] . PDE4 inhibition (rolipram) reduces BBB damage in ischemic stroke in mice [318] . Caffeine and theobromine are adenosine receptor antagonists [319] . Extracellular adenosine increases BBB permeability and adenosine receptor antagonism blocks the entry of inflammatory cells and soluble factors into the brain [320] Folic acid Vitamin B12-B6-folate treatment improves BBB function in patients with hyperhomocysteinemia and mild cognitive impairment [321] . Folic acid decreases BBB leakage and reactive astrogliosis following seizures in pregnant and prepubertal rats [322] (Continued) Estrogen protects against BBB breakdown in animal models of stroke or following LPS challenge and maintains barrier integrity [324] [325] [326] [327] Components of the Mediterranean diet Omega-3 fatty acids reduce BBB disruption in hypoxic/ischemic brain injury [328] . Fish oil reduces BBB disruption in a rat model of juvenile traumatic brain injury [329] . Virgin olive oil reduces BBB permeability following middle cerebral artery occlusion in rats [330] . Aged garlic extract protects against BBB disruption caused by a high saturated fatty acid diet in mice [331] . Resveratrol, a component of grape and red fruit skins, and red wine [332] , maintains the integrity of the BBB after cerebral ischemia reperfusion in rats [333] Statins