Molecular drug pump may help reduce risk of Alzheimer's

A molecule that has long been an obstacle to cancer chemotherapy and drug treatments for brain disorders may soon become an ally in the fight against Alzheimer's disease, according to researchers at Washington University School of Medicine in St. Louis and the University of Rochester.

In studies in genetically modified mice, scientists found that the molecule, P-glycoprotein (Pgp), accelerates clearance from the brain of amyloid beta (A-beta) peptide, the primary component of the plaques that are the hallmark of Alzheimer's disease.

According to scientists, the new link is potent and intriguing enough to suggest several potential follow-up studies, including investigations of how pharmaceuticals might affect Alzheimer's risk by altering Pgp activity levels.

"We would never claim that Pgp activity is the single critical causative factor in Alzheimer's disease, just like there isn't any single cause of heart attacks, hypertension or cancer," says author David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "But our evidence suggests that it may be one of the more significant risk factors so far identified."

The Journal of Clinical Investigation will publish their results online on Oct. 20.

Scientists are already familiar with a variety of drugs that can promote and suppress Pgp activity. The new connection may, for example, explain a puzzling study that suggested the antibiotic rifampin could slow the decline of patients with mild to moderate Alzheimer's.

"That result didn't seem to be linked to the drug's antibiotic properties, and now we have a much more appealing explanation: rifampin is a known inducer of Pgp activity," says co-author David Piwnica-Worms, M.D., Ph.D., professor of molecular biology and pharmacology and of radiology at Washington University. "Researchers will likely be evaluating this drug and other known Pgp promoters as potential ways to reduce risk." '"/>

Contact: Michael C. Purdy
Washington University School of Medicine

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