Two Cardiovascular Proteins Pose A Double Whammy In Alzheimer's

December 23, 2008

Adapted from the University of Rochester Medical Center

Researchers have found that two proteins that work in tandem in the brain's blood vessels present a double whammy in Alzheimer's disease. Not only do the proteins lessen blood flow in the brain, but they also reduce the rate at which the brain is able to remove amyloid beta, the protein that builds up in toxic quantities in the brains of patients with the disease.

The work, described in a paper published online December 21, 2008 in the journal Nature Cell Biology, provides hard evidence directly linking two processes thought to be at play in Alzheimer's disease: reduction in blood flow and the buildup of toxic amyloid beta. The research makes the interaction between the two proteins a seductive target for researchers seeking to address both issues.

Scientists were surprised at the finding, which puts two proteins known for their role in the cardiovascular system front and center in the development of Alzheimer's disease.

"This is quite unexpected," said Berislav Zlokovic, M.D., Ph.D., a neuroscientist and a senior author of the study. "On the other hand, both of these processes are mediated by the smooth muscle cells along blood vessel walls, and we know that those are seriously compromised in patients with Alzheimer's disease, so perhaps we shouldn't be completely surprised."

The new findings are the result of a seven-year collaboration between two laboratories. Zlokovic heads the Center for Neurodegenerative and Vascular Brain Disorders, looking at molecular roots of diseases like Alzheimer's. Several years ago, after he found that several genes well known to cardiovascular researchers seemed to be especially affected in Alzheimer's patients, he turned to Joseph Miano, Ph.D. to help analyze the findings. Miano is interim director of Aab Cardiovascular Research Institute and associate professor of Medicine, and he is senior co-author of the new study.

Normally, amyloid is picked up efficiently by blood vessels that then whisk the toxic trash away. But in Alzheimer's disease, the system no longer is able to keep up with the body's production of the substance. The molecular trash accumulates, and Zlokovic and others believe the buildup kills brain cells.

The current work focuses on two proteins well known to cardiovascular researchers. Together they act as a master switch that determines whether smooth muscle cells contract—one of many ways the body controls just how much blood is flowing in the body.

Two years ago, Zlokovic and Miano published a study showing that the two proteins are much more active in the blood vessels of brains of people with Alzheimer's disease than in people who do not have the disease. They showed that when they reduced the activity of the proteins, blood flow in the brain increased, and when the genes were more active, blood flow decreased. The latest report goes further, implicating the molecular duo in the slowed removal of amyloid beta.

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