Berg Brain Entry and Exit Consortium: Identifying the Blood-Brain Barrier Changes During Alzheimer’s Disease

Alzheimer’s disease (AD) is a debilitating chronic neurodegenerative disease that is the leading cause of dementia and involves memory loss, disorientation, language issues, mood swings and many other behavioral abnormalities. Recently, it has been suggested that dysfunction of the blood-brain barrier (BBB) may be an important component of the pathogenesis of AD; however, very little is known about how the BBB may change in patients with AD. We were able to determine the molecular changes to the BBB in patients with AD, identifying many novel changes to the BBB that may affect the function of the BBB and the progression of AD. In addition, because patients with AD display neuronal hyperactivity as well as loss of circadian functions, we aimed to determine how both neuronal activity regulates the BBB, and whether there is a circadian oscillation of the BBB. We have identified that neuronal activity downregulates the key BBB efflux transporter P-glycoprotein (PGP), which is important for the removal of amyloid beta from the brain through modulation of the vascular circadian clock. Therefore, neuronal hyperactivity and loss of circadian function may act on the BBB to exacerbate the buildup of amyloid in the brain.