Brain Blood Flow, Alzheimer Linked

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Brain Blood Flow, Alzheimer Linked

January 26, 1999

NEW YORK (AP) - 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 may also 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.

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, 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, 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 render 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.

Iadecola said a 1997 study of Alzheimer patients found that vitamin E, an

antioxidant, modestly slowed the course of the disease.