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Studies find genes, diet have role in Alzheimer’s

Mon., Aug. 15, 2005

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, a scientific journal. “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 that is critical in ridding the body of the amyloid.

Zlokovic said the animal studies point to the vascular system as the first failed defense in Alzheimer’s disease.

He believes that vascular changes could begin early in life and that the system in old age could just be “worn out.”

This makes the folic acid story more intriguing.

The journal Alzheimer’s & Dementia recently reported findings from the Baltimore Longitudinal Study of Aging. Among 579 men and women older than 60 who did not have dementia, those with an average diet of 400 micrograms of folic acid had a 55 percent reduced risk of developing Alzheimer’s, scientists said.

Folic acid has been shown to lower homocysteine.


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