Inflammation in brain may trigger Alzheimer’s disease
15 July 2009
The anti-inflammatory drug indomethacin could hold promise as a
treatment for Alzheimer’s disease, says a Saint Louis University doctor
Two research studies published by William A Banks, professor of
geriatrics and pharmacological and physiological science at Saint Louis
University School of Medicine in the US, support this conclusion and
offer what he calls a “one-two punch” in giving clues on how Alzheimer’s
disease develops and could be treated.
His study in the July edition of the Journal of Alzheimer’s
Disease supports the idea that toxic levels of amyloid beta
protein, the substance scientists believe is responsible for Alzheimer’s
disease, accumulate in the brain because a pump that pushes it into the
blood and past the blood-brain barrier malfunctions.
The blood-brain barrier is a system of cells that regulates the
exchange of substances between the brain and the blood. The blood-brain
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
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
anti-inflammatory medication, as a buffer to protect LRP from being
Inflammation, which is part of the body’s 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 Alzheimer’s disease are seeing in
their clinical practice.
“Nonsteroidal anti-inflammatory drugs, especially indomethacin, have
been associated with protection against Alzheimer’s disease. Our work
could influence that debate and thinking at the patient-care level,”
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