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HONOLULU, Dec. 18, 2000 - Researchers believe that a chemical called methionine plays a role in Alzheimer's disease and also could explain how vitamin E slows the progress of the disease in its later stages. The finding could lead to new drugs to delay the advance of Alzheimer's, say the researchers, who presented their study today during the 2000 International Chemical Congress of Pacific Basin Societies.

The weeklong scientific meeting, held once every five years, is hosted by the American Chemical Society, in conjunction with its counterparts in Australia, Canada, Japan and New Zealand.

Alzheimer's is a chronic form of dementia that primarily strikes the elderly and causes severe memory loss and, eventually, death. The disease is characterized by the overproduction of a protein, beta-amyloid, that accumulates in the brain of its victims. Although normal brains contain beta-amyloid, those with the disease have comparatively large amounts. The protein is thought to produce chemicals called free radicals, which are toxic to the brain, according to the study's lead researcher, Allan Butterfield, Ph.D., a professor of chemistry and director of the Center for Membrane Sciences at the University of Kentucky in Lexington.

Butterfield examined the sequence of amino acids in beta-amyloid and found that one in particular - methionine - is the likely source of the toxic free radicals. He then modified methionine by substituting a sulfur atom with a carbon atom. In laboratory tests using rat brain cells, the modified version did not produce free radicals or kill brain cells, according to the researcher.

To determine whether the laboratory results could translate to living organisms, Butterfield joined forces with Christopher D. Link, Ph.D., a researcher at the University of Colorado's Institute for Behavioral Genetics in Boulder, Colo. The researchers obtained genetically modified worms that were able to produce either normal human beta-amyloid or methionine-substituted amyloid. The worms making normal beta-amyloid produced free radicals, which caused damage to the worm muscle proteins. The worms making methionine-substituted amyloid did not produce free radicals; hence, there was no damage to the muscle proteins.

Recent studies have demonstrated that higher than normal doses of vitamin E may slow the advance of Alzheimer's in some people with late stages of the disease. The current study provides a possible explanation for this link. Vitamin E, an antioxidant, appears to work by destroying free radicals (oxidants) produced by amyloid, says Butterfield.

"Our research provides an important insight into this mechanism and offers an appropriate rationale for antioxidant intervention in Alzheimer's," says Butterfield.

The finding provides yet another clue in unraveling the complex mystery of Alzheimer's. A growing number of factors have been associated with the disease, including stress, prior head injury, viruses, genes and abnormal concentrations of metal ions in the brain, including aluminum, zinc, copper, iron, mercury and lead.

In addition to drugs, vaccines and gene therapy are promising targets for treating the disease, which affects an estimated 4 million people in the United States. Unless better treatments are found, that figure is predicted to rise to 14 million later this century, says Butterfield, who calls Alzheimer's a potential public health crisis.

More than 8,000 research papers will be presented during this year's International Chemical Congress, which is sponsored jointly by the American Chemical Society (American Chemical Society), the Chemical Society of Japan, the Canadian Society of Chemistry, the Royal Australian Chemical Institute and the New Zealand Institute of Chemistry.

The paper on this research, MEDI 572, will be presented at 11:05 a.m., Monday, Dec. 18, at the Hilton Hawaiian Village, South Pacific Ballroom III, Mid-Pacific Conference Center, during the symposium, "Alzheimer's Disease: Receptors and Small Molecule Therapies."

Allan Butterfield is a professor in the department of chemistry at the University of Kentucky in Lexington, Ky.

Christopher D. Link is a research scientist in the Institute for Behavioral Genetics at the University of Colorado in Boulder, Colo.

The National Institute on Aging and the state of Kentucky supported the study.