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By Jacqueline Stenson
Medical Tribune. April 4, 1996.
A protein associated with the development of Alzheimer's disease may cause mental deterioration by unleashing free radicals in the brain, Florida researchers report.
The protein beta amyloid has long been thought to be involved in Alzheimer's disease because it is found deposited in the brains and blood vessels of people with the condition. But scientists have not been able to determine how the protein contributes to brain-cell damage.
Now, new research suggests that amyloid generates the release of free radicals, which constrict blood vessels and prevent blood flow to brain cells. Free radicals also may damage neurons directly, researcher Michael J. Mullan, M.D., Ph.D., professor of biological psychiatry at the University of South Florida College of Medicine in Tampa, reported in Nature (1996;380:168-171).
"Understanding the role of blood vessels in Alzheimer's disease brings us closer to identifying a way of delaying onset or slowing the rate of disease progression," Dr. Mullan said. "Because it is easier to deliver drugs to blood vessels than to neurons, this finding may open new avenues of treatment."
The researchers based their findings on laboratory studies of blood vessels from rats. When they added small amounts of beta amyloid, they found that the protein interacted with the endothelium of the vessels, producing an excess of toxic free radicals, which led to vessel constriction, according to the researchers. But when they pre-treated the vessels with superoxide dismutase (an enzyme that removes excess oxygen free radicals) and then beta amyloid, the vessels did not constrict.
Beta amyloid may lead to increased production of oxygen free radicals, which damage endothelium and increase vasoconstriction, the researchers explained.
"This finding provides a link between the amyloid theory of Alzheimer's disease and the free radical theory of aging and degeneration," Dr. Mullan said.
In the development of Alzheimer's disease, beta amyloid is thought to interact with apolipoprotein E (Apo E) to cause the buildup of beta amyloid deposits in the brain.
Apo E also is considered a risk factor for ischemic blood-vessel disease, Dr. Mullan said, and this, along with the new findings, suggests that damage to the vascular system in the brain contributes to Alzheimer's disease.
"This work is interesting and provocative, and it gives doctors another line of attack in the problem of Alzheimer's disease," said Zaven Khachaturian, Ph.D., director of the Alzheimer's Association's Ronald and Nancy Reagan Research Institute and former director of Alzheimer's disease research at the National Institute on Aging.
In an accompanying article in Nature, Jonathan Stamler, M.D., of the department of cell biology at the Duke University Medical Center in Durham, N.C., suggested that increased deposition of beta amyloid in the brain also may hinder endothelial production of nitric oxide molecules, which enable blood vessels to dilate normally. "Treatment might include [nitric oxide] supplementation," he wrote, if a deficit of nitric oxide is found to play a causative role in neurodegeneration.