The new findings are the product of a five-year collaboration between two types of scientists that traditionally don't work closely together: neuroscientists who focus on the brain, and cardiovascular experts who put most of their focus on the heart.
The first step in the study came when Zlokovic's team compared the activity of genes in the brain from several people with Alzheimer's who had died, to that of several people without the disease who had died. It's a type of study widely done now by scientists looking at a host of diseases, using vast gene arrays that can tell how active thousands of genes are in a part of the body.
As Zlokovic perused the list of genes whose activity differed depending on whether the person had Alzheimer's or not, he recognized that several play a role in constricting the arteries. He asked colleague Joseph Miano, Ph.D., a cardiovascular researcher and expert on the smooth muscle that makes up part of the arteries, to take a look.
Miano recognized the group as genes that are all controlled by one of two master regulators of gene activity in smooth muscle cells. Those proteins, myocardin and SRF (serum response factor), are well known for the control they exert on blood vessel walls. Working together, the two are the chief players that regulate how much the smooth muscle cells inside the arteries contract. The more the cells contract, the narrower the artery becomes, and the less blood that flows.
In a series of experiments carried out together by Miano's and Zlokovic's students and colleagues, the teams demonstrated the power of the genes in the brain.
First they confirmed that both genes are more active in the brains of Alzheimer's patients than they are in the brains of people without the disease. They also found that
Contact: Tom Rickey
University of Rochester Medical Center