Nicotine By-Product May Block Alzheimer's

Adding chemical to sugar leads to fewer protein clusters in lab

(HealthDay is the new name for HealthScoutNews.)

MONDAY, June 16, 2003 (HealthDayNews) -- A broken-down form of nicotine seems to prevent the formation of the protein thickets implicated in Alzheimer's disease.

The substance, called nornicotine, joins up with sugar and binds to the potentially harmful proteins in such a way that they can no longer clump, a new study says.

But don't think nicotine's your best friend. Aside from being highly addictive, the substance is toxic to cells. Still, the researchers say the new finding should help guide further studies with nicotine substitutes designed to avoid the harm and preserve the benefits of the molecule.

"We could try to look at similar structures that don't have the toxicity or addictive problems" associated with nicotine, says study co-author Kim Janda, a chemist at the Scripps Research Institute in La Jolla, Calif. A report on the work appears this week in the Proceedings of the National Academy of Sciences.

An estimated 4 million Americans suffer from Alzheimer's disease, a brain wasting disorder with no cure. The Alzheimer's Association projects that number will reach 14 million by the middle of the century.

Although it's still a matter of debate, many researchers generally believe that Alzheimer's disease is caused by sticky protein fibers, or plaques, that gradually spread over healthy brain cells. Plaques consist of a substance called beta-amyloid. A major focus of Alzheimer's research is to block the clustering of amyloids.

Some population studies have hinted that heavy smokers may be less prone than nonsmokers to Alzheimer's disease, and that somehow nicotine delays the onset of the illness. More recent research has questioned those results, says Nigel Greig, a pharmacologist who studies Alzheimer's disease at the U.S. National Institutes of Health's Gerontology Research Center in Baltimore. "The epidemiological studies are no longer quite so forceful," Greig says.

Janda and his Scripps colleague, Tobin Dickerson, combined nornicotine, glucose and beta-amyloid in test tubes to see what would happen. In the presence of the two other molecules, beta-amyloid clumping fell by about 20 percent, they found.

Analysis of the chemical reaction showed that nornicotine and glucose attach themselves to beta-amyloid in a process called glycation, which (minus the nicotine) is also involved in the browning of food. By doing so, they change the structure of the brain proteins in a way that force them to slide by each other without hooking up. "They just can't come together," Janda says.

Glycated proteins are targeted for removal by cell cleanup systems, he says.

Michael Zagorski, a chemist at Case Western Reserve University in Cleveland, calls the study "a great starting point" for additional research. However, Zagorski -- who in earlier work speculated that nicotine might tie up beta-amyloid -- says it's a big leap from test tube to brain.

Scientists would have to find beta-amyloid in the brain that had been modified by the nicotine-glucose bond, he says: "If they found it, then that would be very significant, but it might not be easy."

Janda says he would like to explore ways to demonstrate that the nicotine mechanism is at work in Alzheimer's. He also hopes to learn if the same reactions explain why some smokers may gain protection from Parkinson's disease, another progressive neurologic ailment. As with Alzheimer's and nicotine, the evidence here is mixed, he adds.

More information

The Alzheimer's Association and the National Institute of Neurological Disorders and Stroke have more on the disease.

SOURCES: Kim Janda, Ph.D., professor, chemistry, Scripps Research Institute, La Jolla, Calif.; Nigel Greig, Ph.D., Gerontology Research Center, Baltimore; Michael Zagorski, Ph.D., associate professor, chemistry, Case Western Reserve University, Cleveland; June 16-20, 2003, Proceedings of the National Academy of Sciences
Consumer News