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Leaky Blood Vessels In The Brain May Lead To Alzheimer's

Leaks in a barrier between blood vessels and brain cells could contribute to the development of Alzheimer's. (Science Source)

Researchers appear to have found a new risk factor for Alzheimer's disease: leaky blood vessels.

An MRI study of found those experiencing mild problems with thinking and memory had much leakier blood vessels in the hippocampus. "This is exactly the area of the brain that is involved with learning and memory," says Berislav Zlokovic, the study's senior author and director of the Zilkha Neurogenetic Institute at the University of Southern California.

The study, published in Neuron, also found that blood vessels in the hippocampus tend to become leakier in all people as they age. But the process is accelerated in those likely to develop Alzheimer's or other forms of dementia.

The finding suggests that it may be possible to identify people at risk for Alzheimer's by looking at their blood vessels, says Rod Corriveau , a program director at the National Institute of Neurological Disorders and Stroke, which helped fund the research. The results also suggests that a drug to help the body seal up leaky blood vessels could delay or prevent Alzheimer's and other forms of dementia.

"This study gives patients and families hope for the future, hope that detecting leaky blood vessels early will provide the opportunity to stop dementia before it starts," Corriveau says.

The new research grew out of earlier studies of people who died with Alzheimer's disease. "We were looking at brains from autopsies and it (became) quite apparent that there is a breakdown of the blood-brain barrier," Zlokovic says.

The blood-brain barrier is a special layer of cells that normally prevents bacteria and toxins that circulate in the bloodstream from mixing with the fluid that surrounds brain cells. When it breaks down, toxins leak into the fluid that surrounds brain cells and eventually damage or kill the cells.

The autopsy research couldn't show whether the breakdown occurred before or after Alzheimer's appeared. So Zlokovic and his team used a special type of MRI to study the living brains of more than 60 people. The group included both healthy individuals and people with mild cognitive impairment, which can be an early sign of Alzheimer's.

The researchers paid special attention to the hippocampus because it is one of the first brain areas affected by Alzheimer's. And they found that in some regions of the hippocampus, the permeability of the blood-brain barrier was more than 50 percent higher in people with mild cognitive impairment.

The finding could help explain why people with atherosclerosis and other problems with their blood vessels are more likely to develop Alzheimer's, says Corriveaux. "There's every reason to think that a lot of Alzheimer's disease does involve vascular damage," he says.

The study also adds to the evidence that amyloid plaques and the tangles known as tau aren't the only factors that lead to Alzheimer's. There are probably several different paths to dementia, Corriveau says, including one that involves leaky blood vessels.

One important question now is whether it's possible to repair damage to the blood brain barrier. That may be possible using cells known as pericytes, which help prevent blood vessels in the brain from leaking.

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AUDIE CORNISH, HOST:

Researchers may have found a new risk factor for Alzheimer's disease. The culprit? Leaky blood vessels in the brain. NPR's Jon Hamilton reports that the finding could eventually help doctors predict and prevent Alzheimer's and other forms of dementia.

JON HAMILTON, BYLINE: Blood vessels in the brain include a special protective layer called the blood-brain barrier. It keeps the bacteria and toxins that circulate in blood from leaking into the brain. A few years ago, some researchers noticed that this barrier is damaged in people who die of Alzheimer's. Berislav Zlokovic is at the University of Southern California.

BERISLAV ZLOKOVIC: We're looking at brains from autopsies, and it becomes quite apparent that there is breakdown of the blood-brain barrier.

HAMILTON: But wasn't clear whether the breakdown was happening before Alzheimer's appeared or after. In other words, was it a potential cause or just byproduct of the disease? To find out, Zlokovic used a special type of MRI to study the brains of more than 60 people. These included both healthy individuals and people with mild cognitive impairment, which can be an early sign of Alzheimer's. Zlokovic says he paid special attention to the hippocampus, one of the first brain areas affected by Alzheimer's.

ZLOKOVIC: There is an increase in the blood-brain barrier breakdown by about 40 to 50 percent in the hippocampus, the brain region that is involved with memory and learning.

HAMILTON: Blood vessels are much leakier in people with cognitive problems. And Zlokovic believes that is exposing their brains to toxic substances.

ZLOKOVIC: Leading to loss of brain cells eventually or loss of connections between different brain cells.

HAMILTON: The hallmarks of Alzheimer's disease. The finding could help explain why people with atherosclerosis and other problems with their blood vessels are more likely to develop Alzheimer's. Rod Corriveau is a program director at the National Institute of Neurological Disorders and Stroke, which helped fund the research.

ROD CORRIVEAU: There's every reason to think a lot of Alzheimer's disease does involve vascular damage.

HAMILTON: Corriveau says the study also adds to the evidence that amyloid plaques and tangles known as tau aren't the only factors that can lead to problems with memory and thinking. He says there are probably several paths.

CORRIVEAU: One of them could be through amyloid. One of them could be through tau. One of them could be through vascular contributions. And in fact, what is more likely is that they are interactions between these and other factors to create dementia, including Alzheimer's disease.

HAMILTON: Corriveau says changes in the blood-brain barrier happen long before mental problems appear so it may be possible to use those changes as markers to predict who will go on to develop Alzheimer's disease. And Corriveau says the disease might be delayed or prevented by drugs that make blood vessels less leaky.

CORRIVEAU: This study gives patients and families hope for the future, hope that detecting leaky blood vessels early will provide the opportunity to stop dementia before it starts.

HAMILTON: The new research appears in the journal Neuron. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.

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