P-Glycoprotein and Alzheimer's Disease

Project Summary

P-glycoprotein (P-gp) is an export pump that is highly active at the barrier that separates brain tissue from blood (called the blood brain barrier or BBB). P-gp can transport amyloid-β (Aβ), a compound that accumulates in the brain of people with Alzheimer's disease (AD). We believe that reduced activity of P-gp at the BBB results in accumulation of Aβ in the brain of patients with AD. In the proposed study we will compare P-gp activity at the BBB in patients with AD and in age-matched volunteers without AD, using a method called positron emission tomography (PET). The proposed studies are particularly relevant to Alzheimer's disease for a number of reasons. For the first time, our studies will test the idea that P-gp activity at the BBB is compromised in AD. If it is, we will test in future studies if compounds that are known to increase P-gp activity in the human intestine, such as rifampin or St. John's Wort, can increase P-gp activity at the BBB. If both or one of these compounds do increase P-gp activity at the BBB, they can be tested for their effectiveness in stopping progression of Alzheimer's disease.