The antiinflammatory drug indomethacin could hold promise as a treatment for Alzheimers disease, says a Saint Louis University doctor and researcher.

Two research studies published by William A. Banks, M.D., professor of geriatrics and pharmacological and physiological science at Saint Louis University School of Medicine, support this conclusion and offer what he calls a “onetwo punch” in giving clues on how Alzheimers disease develops and could be treated.

His study in the July edition of the Journal of Alzheimers Disease supports the idea that toxic levels of amyloid beta protein, the substance scientists believe is responsible for Alzheimers disease, accumulate in the brain because a pump that pushes it into the blood and past the bloodbrain barrier malfunctions.

The bloodbrain barrier is a system of cells that regulates the exchange of substances between the brain and the blood. The bloodbrain barrier transporter known as LRP is the pump that removes amyloid beta protein from the brain and into the bloodstream.

“LRP malfunctions like a stop light stuck on red, and keeps amyloid beta protein trapped in the brain,” said Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis.

He tested the hypothesis by giving mice an antisense, which is a molecular compound that blocked the production of LRP. Amyloid beta protein accumulated in the brain and the mice showed memory loss and learning impairment.

The finding raises the question of what causes LRP to malfunction. Banks study in the May issue of Brain Behavior and Immunity suggests inflammation as the culprit and supports using indomethacin, an antiinflammatory medication, as a buffer to protect LRP from being turned off.

Inflammation, which is part of the bodys natural immune response, occurs when the body activates white blood cells and produces chemicals to fight infection and invading foreign substances.

“We induced inflammation in mice and found that it turned off the LRP pump that lets amyloid beta protein exit the brain into the bloodstream. It also revved up an entrance pump that transports amyloid beta into the brain. Both of these actions would increase the amount of amyloid beta protein in the brain.”

Banks then gave mice indomethacin, which prevented inflammation from turning off the LRP (exit pump).

His findings help to explain what doctors who are studying the use of indomethacin to treat people with Alzheimers disease are seeing in their clinical practice.

“Nonsteroidal antiinflammatory drugs, especially indomethacin, have been associated with protection against Alzheimers disease. Our work could influence that debate and thinking at the patientcare level,” Banks said.

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