December 26, 2003

Radical News on Alzheimer's

In what may be a significant step forward in the understanding of Alzheimer's Disease, researchers at Ohio State University have found new clues to how free radicals can contribute to the disease.

They found that oxidation, a type of damage to cells caused by free radicals, can damage certain kinds of messenger RNA in the brain and that damage may be related to Alzheimer's.

Free radicals are unstable atoms or atom groups within the body that can disrupt nearby cells. Some free radicals are created as part of the body's normal metabolism. However, they can also be created by environmental factors such as pollution, radiation, cigarette smoke and herbicides.

In an Alzheimer's sufferer's brain, much of the mRNA is damaged by oxidation. It is thought that oxidized mRNA processes proteins abnormally, leading to the death of vital neurons.

So-called messenger RNA, or mRNA, turns DNA's genetic code into the proteins needed for healthy brain function. But in an Alzheimer's sufferer's brain, much of the mRNA is damaged by oxidation. It is thought that oxidized mRNA processes proteins abnormally, leading to the death of vital neurons.

"We know that free radicals can damage DNA, but nobody had looked at the effect of free radicals on RNA," said C. Glenn Lin, the study's lead author and an assistant professor of neuroscience at Ohio State. "When we looked for mRNA in the Alzheimer's brain, we found significant amounts of oxidized mRNA in the frontal cortex, which is one of the main areas affected by the disease."

This is the first study to describe the specific types, or species, of mRNA oxidized in Alzheimer's disease; until this point, researchers knew that the oxidation of mRNA played a role in Alzheimer's disease, but they did not know which species were implicated.

Asked to comment on the study, TheDoctor's gerontology expert, Dr. John Morley, Dammert Professor of Gerontology, Saint Louis University Medical School and Director of the Geriatric Research Education and Clinical Center at the St. Louis V.A. Medical Center, said, "Free radical damage is a well recognized component of Alzheimer's disease. The news here is that free radicals can cause oxidation damage to RNA in Alzheimer's; this suggests an actual mechanism by which they may cause memory deterioration. Studies such as this should eventually lead to much better insight into the causes of Alzheimer's disease."

The researchers used tissue taken from the brains of 11 recently deceased Alzheimer's patients (aged 65 to 86); seven age-matched controls; and two young control subjects (aged 22 and 49). They analyzed mRNA content from the hippocampus, frontal cortex and cerebellum of each person's brain, looking for mRNA transcripts - replicas of DNA genetic code - to see if certain transcripts were more susceptible to oxidation.

The researchers found high levels of oxidation damage in the frontal cortex of only the Alzheimer's patients' brains. They also found that only certain mRNA species were oxidized.This oxidation appears to start early in the disease process, Lin said, and the disease progressively worsens as proteins continue to accumulate.

Lin said he hopes that some day researchers will be able to pinpoint the exact kinds of mRNA transcripts that cause protein aggregation.

"That might help us figure out what kind of proteins in the cell go haywire at an early stage of Alzheimer's," he said. "Then, if we can somehow block that process, perhaps we could reduce the progression of the disease."

Reviewed by: John E. Morley, M.D..
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