Now you see 'em ... amyloid plaques are visible in untreated brain tissue from an Alzheimer's patient (left), but not after treatment with naproxen (right).

Pain Relievers Thwart Alzheimer's Lesions

People who routinely take the pain relievers ibuprofen and naproxen for arthritis and other conditions are substantially less likely to develop Alzheimer's disease. Now, a new study helps explain why: The drugs dissolve the disease's hallmark destructive protein fragments, known as amyloid plaques. The research, to be published in the 31 March issue of Neuroscience, may lead to strategies for preventing or slowing the course of the disease.

Epidemiological studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen may prevent or delay Alzheimer's by reducing brain inflammation that leads to nerve damage. But experts have not recommended that people at risk start popping pills, because they haven't been able to pin down a mechanism that explains how NSAIDs curb the diseases. In addition, chronic use of some NSAIDs can cause internal bleeding and other side effects.

Jorge Barrio, a chemist at the University of California, Los Angeles, and colleagues suspected that NSAIDs can directly interact with the amyloid plaques that are believed to kill neurons in Alzheimer's patients. They treated brain tissue samples from a deceased patient with one of several anti-inflammatory drugs, then added a recently developed chemical marker called FDDNP, which glows when it binds to amyloid. They found that some NSAIDs--naproxen and two forms of ibuprofen--blocked FDDNP from binding to the plaques, indicating that the drugs themselves had already latched on. In a second experiment, Barrio's team cultivated synthetic amyloid in a test tube. They found that ibuprofen and naproxen inhibited plaque formation and dissolved existing plaques.

Understanding NSAIDs' molecular action should help researchers tweak existing drugs to maximize both anti-inflammatory and anti-amyloid effects and to minimize side effects, says pharmacologist William Thies of the Alzheimer's Association in Chicago. In addition, he says, by identifying a chemical marker--FDDNP--that can detect minute changes in -amyloid, the new research could lead to more sensitive brain scanning techniques for tracking the disease and evaluating treatments. Nevertheless, Thies cautions, "we're a long way from the end of the story, and we'll just have to wait and see whether this leads to significant clinical advances."

Related sites
Jorge Barrio's Web site
Anti-Inflammatory Therapy Fact Sheet, from the Alzheimer's Association
Alzheimer's Disease Information Center, from Infoaging.org

Posted in Brain & Behavior