Blood Protein Linked To Age-Related Memory Loss

One frustrating part of getting older is memory loss—forgetting where you put the TV remote, not remembering the name of the family that used to live next door.

A new study in mice suggests that a protein that circulates in the blood and has levels that increase with age could be one culprit behind this mental decline. Finding ways to reduce the protein in the body could lead to therapies that prevent or reverse age-related memory loss, the researchers say.

“It’s a very impressive paper and a major advance in our understanding of cognitive aging,” says Scott A. Small, a neurologist at Columbia University who was not involved in the study.

The new work stems from a series of studies looking at molecules in blood associated with aging. Researchers, including Tony Wyss-Coray of Stanford University, have shown that transferring blood from young mice into old mice can reverse age-related loss in cognitive function. And the effect goes both ways: Blood from old mice can impair memory in young ones.

Saul A. Villeda, a former postdoc in the Wyss-Coray lab and now a professor at the University of California, San Francisco, wanted to study a blood factor implicated in those previous studies as contributing to the aging process—β2-microglobulin (B2M). Scientists have known that this protein plays a role in pruning nerve cell connections in young, developing brains.

In the new study, the researchers found that injecting B2M into the brains of young mice led to poor performance in tests of two types of memory compared with animals that didn’t receive the protein. But the effects weren’t permanent. If the researchers waited 30 days after the B2M injections and then ran the memory tests, the young mice showed no memory deficit.

To determine the effects of removing B2M, the team engineered the mice to knock out the gene for the protein. With age, these animals showed less memory dysfunction than nonengineered mice of the same age (Nat. Med. 2015, DOI: 10.1038/nm.3898).

“The implication here is if you could reduce B2M in humans, you could reverse age-related memory decline, which would be profound,” Small says.