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Studies Link Blood Vessel Health, Alzheimer's

Posted on: Tuesday, 16 August 2005, 06:00 CDT

A gene that regulates blood vessel health in the brain may not be doing its job in people with Alzheimer's disease, according to a new study.

At the same time, an unrelated study has found that folic acid might reduce the risk of Alzheimer's by lowering homocysteine, an amino acid that at high levels is associated with cardiovascular problems.

"There are many signs pointing to the vascular system in Alzheimer's," said Dr. Berislav Zlokovic, a professor of neurosurgery and neurology at the University of Rochester Medical Center and author of the new gene finding in Nature Medicine. "These findings should stimulate more research in this area."

Zlokovic and colleagues took snippets of brain tissue from 36 autopsies -- 11 of the deceased had Alzheimer's -- and put them through a machine that reads levels of gene activity. In the brain tissue of those who had Alzheimer's, one gene was almost totally inactive. "It was barely detectable," Zlokovic said.

He suspects that, without this gene's involvement, the brain's vascular system is not functioning up to par. To test his theory, he reduced the ability of the gene to make protein in a new generation of mice and found that the animals had dramatically lowered blood flow. Their brains also had difficulty removing a sticky substance called amyloid, which clumps into disease-causing lesions in the brains of Alzheimer's patients. The animals also had behavior changes, specifically learning and memory problems.

When the same gene, called MEOX-2, was transplanted back into the animals, new blood vessels formed, and cells recovered the ability to form proper capillary networks. These networks were also making a lipoprotein receptor critical in ridding the body of the amyloid substance.

Zlokovic said the animal studies point to the vascular system as the first failed defense in Alzheimer's disease. He believes that these vascular changes could begin early in life and that the system in old age could just be "worn out."

Almost five decades ago scientists at Johns Hopkins University began studying 1,400 people as they aged. Funded by the National Institutes of Health, the Baltimore Longitudinal Study of Aging is now managed countrywide at several institutions. They recently analyzed diets of 579 men and women older than 60 who did not have dementia. They were followed for an average of nine years and then split into two groups: those diagnosed with Alzheimer's and those who hadn't been. The results were reported in the journal Alzheimer's & Dementia.

Those who reported an average diet of 400 micrograms of folic acid had a 55 percent reduced risk of developing Alzheimer's, the scientists said.

Source: Cincinnati Post

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