Originally created 01/26/99

Blood flow connected to disease



NEW YORK -- Rogue bits of a natural protein may promote Alzheimer's disease by disrupting the flow of blood in tiny vessels of the brain, a study suggests.

The study provides more evidence that vitamin E and other antioxidants may fight the disease, and suggests that finding treatments to restore normal blood flow also may pay off.

Scientists don't know what causes most cases of Alzheimer's. Many point to overproduction of natural protein fragments called amyloid-beta, which form clumps in the brains of patients. Studies show these fragments can kill brain cells.

The new work suggests amyloid-beta, or related fragments, can promote Alzheimer's in a second way: by boosting production of harmful substances called oxygen radicals, which in turn keep tiny blood vessels from delivering the right amounts of blood to brain cells.

The study is presented in the February issue of the journal Nature Neuroscience by neurologist Dr. Constantino Iadecola of the University of Minnesota with colleagues there and elsewhere.

A 1997 study of Alzheimer's patients found that vitamin E, an antioxidant, modestly slowed the course of the disease.

Dr. Zaven Khachaturian, senior medical and scientific adviser to the Alzheimer's Association, called the work exciting and said it reveals "a very important part of the story" of what causes the disease.

In the brain, amyloid-beta fragments are clipped from long proteins called APP. The researchers studied a strain of mice that overproduce APP, which leads to an overproduction of amyloid-beta. Mice from this strain eventually develop mental problems resembling Alzheimer's.

In the latest study, the mice were studied long before any Alzheimer's-type symptoms appeared. Researchers found that microscopic blood vessels in the mice brains didn't respond to a chemical signal to dilate, which would increase blood flow. In normal life that might mean the vessels can't shunt more blood to brain cells when they need it, Dr. Iadecola said.

Eventually that could damage those starved cells, or at least make them more vulnerable to damage from other causes, he said.

But because the mice produce other fragments of APP in excess, the study can't formally show that amyloid-beta is the cause of the brain troubles in the mice, Dr. Iadecola said.

The researchers found two bits of evidence that oxygen radicals were involved in the blood vessel problem.

Researchers were able to prevent the abnormality by bathing the brain with an antioxidant, which renders oxygen radicals harmless. In addition, mice that were programmed genetically to overproduce an antioxidant in addition to APP didn't show the abnormality in the first place.