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Coaxing the Brain's Trashmen Back to Work

Findings may lead to Alzheimer's treatments

THURSDAY, May 17, 2001 (HealthDayNews) -- Imagine a bustling city. One day, the trash collectors go on strike.

After a while, the garbage piles up. Disease spreads and people get sick. If relief doesn't come, the city will crawl to a halt.

This is what happens to the brain of someone with Alzheimer's disease. Pathways become clogged by waste, and nerve cells die off.

But researchers in California think they've discovered a chemical that kicks the brain's lagging garbagemen into gear. While they're preliminary, the findings could someday lead to a treatment for humans.

"If we can boost [the trash collectors] a little bit, we may actually get the system to work again," says Tony Wyss-Coray, an investigator at the Gladstone Institute of Neurological Disease.

Alzheimer's is one of the most destructive and little understood diseases confronting health experts. It affects an estimated one in 10 people older than 65, and nearly half of those over 85. It's expected to become even more prevalent as the U.S. population lives longer and baby boomers become senior citizens.

The disease kicks in as the brains of victims become clogged by bits of protein called "plaque" that are normally processed and harmlessly removed.

In the cardiovascular system, plaque refers to the substances that clog arteries, reducing circulation. In the brain, however, plaque is more like a "toxic waste dump that starts poisoning the neighborhood around it," says Dr. James Grisolia, a neurologist at Scripps Mercy Hospital in San Diego.

Nerve cells die off and the brain descends into dementia, among the most devastating symptoms of Alzheimer's.

Wyss-Coray and fellow researchers studied mice, which can get their own form of Alzheimer's. Some mice were genetically engineered to produce a molecule known as TGF-b1.

The molecule inspired the brains in the mice to work harder to remove "gunk," says Wyss-Coray, who called the effect "dramatic."

"We think we probably tweaked the system to become more efficient at removing junk in the brain," he says.

The findings appear in the current issue of the journal Nature Medicine.

But researchers aren't rushing to inject the molecules into the brains of humans. The molecules are like orchestra conductors, and interfering with how they work could spell disaster for the entire brain, Wyss-Coray says.

Instead of focusing on the molecules, the researchers want to figure out exactly how they spur the trash collectors to action, he says.

Plenty of questions remain. It's still not clear why some older people lose their ability to clear away plaque in the brain, he says. The "junk" piles up in some people without effect, while others lose brain function.

And the researchers want to spend more time studying how the molecule assists the brain by boosting inflammation. By contrast, some Alzheimer's researchers are hoping to treat the disease by reducing inflammation through the use of drugs like ibuprofen, Wyss-Coray says.

Future research will examine how the two approaches could work together, he says.

What To Do

To learn more about Alzheimer's, check the Alzheimer's Disease Education and Referral Center, the Alzheimer's Association, and the National Institute of Neurological Disorders and Stroke.

Or read these other HealthDay stories on Alzheimer's.

For news on clinical trials of Alzheimer's, try Veritas Medicine.

SOURCES: Interviews with Tony Wyss-Coray, Ph.D., investigator, Gladstone Institute of Neurological Disease and assistant professor of neurology, University of California at San Francisco; and James Grisolia, M.D., chairman, Neurology Section, Scripps Mercy Hospital, San Diego
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