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Do ‘Leaky’ Blood Vessels Contribute to Alzheimer’s?

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Brain scans of people at high risk for Alzheimer’s suggest that damage to blood vessels in the brain may play a role in the development of the disease. The findings point to the importance of blood vessel health for healthy brain function and underscore the need for continued research to understand why Alzheimer’s develops, and how it might be cured.

Using a special type of MRI scan, scientists at the University of Southern California’s Keck School of Medicine found that people with memory and thinking problems tended to have “leaky” blood vessels in the hippocampus, a part of the brain critical for learning and memory. The hippocampus is among the first brain areas to degenerate in Alzheimer’s disease.

Normally, the blood vessels in the brain form a tight barrier, preventing toxins and large molecules from flooding the brain, while allowing oxygen and nutrients in. But as people age, the researchers found, this blood-brain barrier starts to break down. The process is accelerated in those in the earliest stages of Alzheimer’s disease.

“This is a significant step in understanding how the vascular system affects the health of our brains,” said the senior author of the study, Dr. Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at USC. “To prevent dementias, including Alzheimer’s, we may need to come up with ways to reseal the blood-brain barrier and prevent the brain from being flooded with toxic chemicals in the blood.”

Earlier autopsy studies of people who had died of Alzheimer’s disease showed damage to the blood vessels in the brain. But scientists weren’t sure if this damage occurred before or after the onset of Alzheimer’s.

So for this study, published in the journal Neuron, the researchers recruited 64 men and women of various ages. They included six healthy young adults, 18 older adults with normal brain function, and 21 older adults with mild cognitive impairment, a form of memory loss that can progress to Alzheimer’s disease. Healthy younger adults with multiple sclerosis, an unrelated central nervous system disorder, were also included for comparison purposes.

Scans of the living brain showed that healthy older people tended to have leakier blood vessels in the hippocampus than younger people. But those with memory and thinking problems who were at high risk of Alzheimer’s had the leakiest blood vessels of all. Blood vessels in other parts of the brain did not show evidence of damage.

The researchers also examined the spinal fluid that flows around the brain and spinal cord. They found that people with memory problems had more proteins in the spinal fluid, further evidence of a breakdown in the blood-brain barrier.

The findings suggest that measurements of blood vessel health in the brain could be used to identify people at risk for Alzheimer’s at its earliest stages, before damage to the brain becomes severe. Potential treatments for Alzheimer’s may be most effective at these early stages, researchers hope, though the search for effective treatments continues.

It’s also possible that drugs could be developed to target the blood-brain barrier and keep it tight. Scientists have identified cells called pericytes that surround blood vessels and help to maintain vascular health in the brain.

“Pericytes are the gatekeepers of the blood-brain barrier and may be an important target for prevention of dementia,” Dr. Zlokovic said. Other studies in animals suggest that damage to pericytes plays a role in Alzheimer’s onset.

The findings could help explain why people with heart and blood vessel disease are also more prone to dementia. Increasingly, scientists recognize the importance of cardiovascular health for a healthy brain. Lifestyle factors such as exercise and a heart-healthy diet appear to promote the health of blood vessels throughout the body, including the brain, and may help to delay the onset of dementia.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Montagne A, Barnes SR, Sweeney MD, et al: “Blood-Brain Barrier Breakdown in the Aging Hippocampus.” Neuron. Jan 21, 2015;85(2): pages 296-302.

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