Scientists Shed New Light on Alzheimer's

Plaques in blood vessels may play key role, too

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By
HealthDay Reporter

FRIDAY, July 22, 2005 (HealthDay News) -- Proteins called amyloid-B peptides that accumulate in plaques around brain cells are known to contribute to Alzheimer's disease, which affects an estimated 4.5 million Americans.

Now, new research suggests that similar peptides accumulating in the blood vessels of the brain contribute to the disease, too. In fact, researchers suspect this blood vessel accumulation may actually lead to plaque formation around neurons -- brain cells -- later on.

"What these new studies show is that the accumulation of amyloid-B in blood vessels is also an important contributing factor to the problems that occur in an Alzheimer's brain," said William E. Van Nostrand, professor of research medicine at Stony Brook University, New York, and the senior author of one of the two studies, both of which are published in the August issue of the American Journal of Pathology.

For years, he said, the general thinking was that amyloid-B accumulates in plaque deposits around the neurons in the brain, leading to problems with memory and other signs of Alzheimer's. Experts have also long known that amyloid-B is found in the brain's blood vessels, but that area had not been a prime focus of research.

"Everyone thought the plaque was causing all the damage," he said.

What the two new studies show, he said, is that accumulation of amyloid in blood vessels is also an important contributing factor in the disease.

Van Nostrand and his colleagues developed a new mouse model genetically engineered to have a mutation in an amyloid protein common to specific Alzheimer's-prone families. "In the people who have this mutation, the mutation causes the amyloid to accumulate," the researcher said. This accumulation occurs in all Alzheimer's patients but it clumps even more in individuals carrying this defect.

"When the mice made that amyloid protein in their brain, they preferentially accumulated this amyloid-beta protein in their brain blood vessels," Van Nostrand explained. "When that happens, a lot of inflammation is associated with it. This shows that the blood vessels [not just neurons] can cause some of these problems."

"In the brains of Alzheimer's patients, you have plaque and blood vessel amyloid," he said. "In this mouse model, we have just blood vessel amyloid. And when you have just the blood vessel amyloid, you can still have the same things you find in an Alzheimer's brain -- inflammation and behavioral impairment."

The finding, Van Nostrand said, shows that blood vessels in the brain should be an important target of Alzheimer's research.

In the second study, conducted by researchers from the U.S. National Institute on Aging and other institutions, two strains of mice engineered to develop dense-core plaques and highly concentrated amyloid-B deposits were used to research the association of blood vessels with amyloid-B deposits.

The researchers found evidence of vessel damage, resulting in the release of protein through the vessel walls and accumulation of the protein next to the vessels. "What their conclusion shows," said Van Nostrand, "is that it appears a lot of these amyloids actually start at the level of the blood vessel and lead to formation of the plaque."

Both studies provide new information that is different from each other, said Dr. Samuel Gandy, a spokesman for the Alzheimer's Association and chairman of the association's medical and scientific advisory council. "Researchers have been trying to understand how the relationship between amyloid in plaque and amyloid in blood vessels are related -- how you can get one and not the other, sometimes both. It was a real conundrum," he said.

As far as practical applications, "I don't see anything you could do right now for a patient [based on the new studies]," said Gandy, who is also director of the Farber Institute for Neurosciences at Thomas Jefferson University, in Philadelphia. "It's a very complicated issue because there is no direct access to the compartment where this material is clumping. It's clumping in between nerve cells and we can't quite get there to wash it out."

More information

To learn more about Alzheimer's disease, visit the Alzheimer's Association.

SOURCES: William E. Van Nostrand, Ph.D., professor, research medicine, Stony Brook University, Stony Brook, N.Y.; Samuel Gandy, M.D., Ph.D., spokesman and chairman of the medical and scientific advisory council, Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; August 2005, American Journal of Pathology

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