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Cholesterol's a Good Guy in the Brain

Helps build nerve connections, study shows

WEDNESDAY, Nov. 7, 2001 (HealthDayNews) -- Cholesterol plays a vital role in building the structure of the brain, researchers report, and that discovery could provide new insights into Alzheimer's disease and other brain disorders.

The finding has nothing to do with the cholesterol that forms dangerous deposits in heart arteries, says Frank W. Pfieger, a scientist at the Max Delbruck-Center for Molecular Medicine in Berlin, Germany, and leader of the researchers who made the discovery. That cholesterol never gets into the brain because of the body's defensive blood-brain barrier.

Pfieger says, "The blood-brain barrier is too tight to let the huge lipoprotein that carries cholesterol through. Ninety percent of the cholesterol in the brain is made there." It is made mostly by glial cells, the cells that nourish and otherwise support the brain's nerve cells.

Pfieger and his colleagues have found that cholesterol made by those cells is needed to form synapses, the specialized sites where one nerve cell is connected to another. Damage to synapses by injury, stroke or a condition such as Alzheimer's disease can cripple brain function.

Earlier work by Pfieger and Ben A. Barres of Stanford University, in California, showed that nerve cells cannot develop synapses on their own, and that something produced by glial cells is essential for the creation and efficient functioning of synapses. Now, researchers at the Berlin center and the Centre de Neurochemie in Strasbourg, France, have identified cholesterol as that something, and they have described the way it works. Their finding is reported in the Nov. 9 issue of Science.

To build synapses, cholesterol must be carried to the appropriate location by another molecule, apolipoprotein E (apoE), the researchers say. Pfieger says this is not surprising because "there is evidence that some form of apolipoprotein is involved in the transport of cholesterol throughout the body."

How cholesterol does its synapse-building work is not known. It might serve as a building material, or it might trigger molecular processes that create the synapses, says Pfieger who plans a series of experiments to answer such questions.

One question involves the role that cholesterol might play in Alzheimer's disease. "Our results imply that genetic or age-related defects in the synthesis, transport or uptake of cholesterol in the central nervous system may directly impair the development and plasticity of the synaptic circuitry," the researchers write.

The link could be with the apolipoprotein E molecule, says Bill Thies, vice president of medical and scientific affairs for the Alzheimer's Association. "A number of studies have shown that a variant form of apoE is associated with more rapid formation of the amyloid deposits of Alzheimer's disease," he says.

The new study "gives us a building block and a theory of how it might work," Thies says. "My prediction is that we will see more of these studies aimed at the link between cholesterol and Alzheimer's disease in the next couple of years."

What To Do

The finding is not a reason to eat more high-cholesterol foods, Thies says. To the contrary, evidence shows that people who take cholesterol-lowering drugs called statins have a lower risk of Alzheimer's disease. That link will be subject of a clinical trial by the National Institute of Aging next year.

For information about Alzheimer's disease, go to the National Institute of Neurological Diseases and Stroke or the Alzheimer's Association.

SOURCES: Interviews with Frank W. Pfieger, Ph.D., group leader, Max-Delbruck Center for Molecular Medicine, Berlin, Germany; Bill Thies, Ph.D., vice president of scientific and medical affairs, Alzheimer's Association, Chicago; Nov. 9, 2001 Science
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