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What's Good for the Joints May Also Prevent Alzheimer's

Arthritis drugs may keep brain plaques from forming, says a new study

WEDNESDAY, Nov. 7, 2001 (HealthDayNews) -- Certain drugs commonly used to counter the pain and inflammation of rheumatoid arthritis also may cut the risk of getting Alzheimer's disease.

In addition to their anti-inflammatory properties, the drugs seem to selectively reduce levels of a harmful protein linked to the neurodegenerative disease, says the study, reported in the Nov. 8 issue of Nature.

About 4 million Americans have Alzheimer's disease, including about 10 percent of people 65 and older, almost half of those 85 and older and half of all patients in U.S. nursing homes.

Early symptoms include mild memory problems -- forgetting names and recent events. As the condition worsens, sufferers may forget where they are and how to perform simple tasks, like eating and swallowing. People with Alzheimer's often become anxious or aggressive, frequently wander off and eventually require round-the-clock care. Progression of the disease varies, from five years to more than 20 years.

Researchers at the University of California, San Diego, in La Jolla, and the Mayo Clinic, in Jacksonville, Fla., report that three types of non-steroidal anti-inflammatory drugs (NSAIDs), including the active ingredient in Advil, markedly reduce production of a protein linked to the amyloid-beta plaque characteristic of Alzheimer's disease. The plaque collects in the brain and interferes with the ability of nerves to communicate with each other.

Although the study looked at effects only in cell cultures and in mice, senior author Dr. Edward Koo, a University of California neurosciences professor, says he's optimistic that the finding could lead to new drugs to fight Alzheimer's disease in humans.

The study developed from research suggesting that people taking certain NSAIDs regularly were less likely to develop Alzheimer's disease. However, the better-known NSAIDs, such as aspirin, Celebrex and Vioxx, had no such effect.

The study showed that ibuprofen, indomethacin and sulindac sulphide lowered the production of the amyloid-beta 42 (AB42) protein, which helps to form the plaque believed to cause Alzheimer's. The three drugs reduced AB42 levels nearly 80 percent in cultured cells.

Ibuprofen reduced AB42 levels in mice by 39 percent, the study says.

Koo says while other compounds have been shown to reduce all AB proteins, the study is the first to identify drugs that selectively target AB42 production.

He says the finding is critical because non-specific drugs could affect certain necessary proteins, including one called Notch that is crucial for brain development.

Since NSAIDs control a complex of inflammatory response enzymes, known as cyclooxygenase (COX), scientists had assumed the drugs inhibited inflammatory changes in the brain. "Our data suggests that that's not the case," says Koo. The reduction in AB42 levels did not involve the COX pathways, he says.

Compounds that bypass the COX pathways could avoid the side effects of current NSAIDs, including gastric bleeding, says Koo.

"The potential is that now we can quickly modify the structures of existing NSAIDs, possibly creating a compound that has a greater effect on AB42 levels at lower doses," says Koo.

If confirmed, the findings could resolve a controversy over how NSAIDs affect Alzheimer's disease, says Dr. Bart de Strooper, an Alzheimer's specialist at the Catholic University of Leuven in Leuven, Belgium, and co-author of an accompanying commentary.

"Now we know why these drugs could be important," he says .

De Strooper says clinical trials over the next two to three years could show that the three drugs might "become a possible treatment in association with other types of drugs."

Koo warns that people shouldn't use NSAIDs to prevent or treat Alzheimer's. "The doses we need to achieve this effect are very high," says Koo. In cell cultures treated with ibuprofen, he says the lowest concentration that had any effect was the equivalent of 16 Advil tablets a day, the highest daily dose approved by the Food and Drug Administration.

What To Do: The Alzheimer's Association, the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease Education & Referral Center provide more information about the disease.

SOURCES: Interviews with Edward H. Koo, M.D., professor, department of neurosciences, University of California, San Diego School of Medicine, La Jolla; Bart de Strooper, M.D., Ph.D., professor, Center for Human Genetics, Catholic University of Leuven, Leuven, Belgium; Nov. 8, 2001, Nature
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