Alzheimer's linked to vascular changes

Folic acid supplements may also reduce risk of disease, study finds

August 15, 2005|By Jamie Talan | Jamie Talan,NEWSDAY

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.

Meanwhile, an unrelated study has found that folic acid supplements may significantly reduce the risk of Alzheimer's. It may do that 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 gene finding in Nature Medicine, a scientific journal. "These findings should stimulate more research in this area."

`Barely detectable'

Zlokovic and colleagues took snippets of brain tissue from 36 autopsies - 11 of the deceased had had Alzheimer's - and put them through a machine that reads levels of gene activity. In the brain tissue of those who had 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 drastically 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 sticky amyloid substance.

Failed defense

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

"If we lower the gene in animals, we get dramatic reductions in blood flow that affect learning and memory," he said. In the lab, it took the animals five minutes to find their way through a tunnel that would normally take an animal 12 seconds, he added.

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

And this makes the folic acid story more intriguing.

Almost five decades ago scientists at the 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 over 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, published by the Alzheimer's Association.

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.

Folic acid can be taken in supplement form and can also be obtained through foods such as oranges, bananas, leafy green vegetables, broccoli, liver, beans and peas. Folic acid has been shown to lower homocysteine.

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