Blocking protein curbs memory loss in old mice

PanARMENIAN.Net - Impeding VCAM1, a protein that tethers circulating immune cells to blood vessel walls, enabled old mice to perform as well on memory and learning tests as young mice, a Stanford study found, Medical Xpress.

Mice aren't people, but like us they become forgetful in old age. In a study published online May 13 in Nature Medicine, old mice suffered far fewer senior moments during a battery of memory tests when Stanford University School of Medicine investigators disabled a single molecule dotting the mice's cerebral blood vessels. For example, they breezed through a maze with an ease characteristic of young adult mice.

The molecule appears on the surfaces of a small percentage of endothelial cells, the main building blocks of blood vessels throughout the body. Blocking this molecule's capacity to do its main job—it selectively latches onto immune cells circulating in the bloodstream—not only improved old mice's cognitive performance but countered two physiological hallmarks of the aging brain: It restored to a more youthful level the ability of the old mice's brains to create new nerve cells, and it subdued the inflammatory mood of the brain's resident immune cells, called microglia.

Scientists have shown that old mice's blood is bad for young mice's brains. There's a strong suspicion in the scientific community that something in older people's blood similarly induces declines in brain physiology and cognitive skills. Just what that something is remains to be revealed. But, the new study suggests, there might be a practical way to block its path where the rubber meets the road: at the blood-brain barrier, which tightly regulates the passage of most cells and substances through the walls of blood vessels that pervade the human brain.

"We may have found an important mechanism through which the blood communicates deleterious signals to the brain," said the study's senior author, Tony Wyss-Coray, Ph.D., professor of neurology and neurological sciences, co-director of the Stanford Alzheimer's Disease Research Center and a senior research career scientist at the Veterans Affairs Palo Alto Health Care System. The lead author of the study is Hanadie Yousef, Ph.D., a former postdoctoral scholar in the Wyss-Coray lab.

The intervention's success points to possible treatments that could someday slow, stop or perhaps even reverse that decline. Targeting a protein on blood-vessel walls may be easier than trying to get into the brain itself.

"We can now try to treat brain degeneration using drugs that typically aren't very good at getting through the blood-brain barrier—but, in this case, would no longer need to," Yousef said.