A brain protein responsible for clearing debris may contribute to the progression of multiple sclerosis and Alzheimer's disease according to 2 studies conducted by researchers at Washington University School of Medicine in St. Louis.
A protein found on the surface of brain cells may be able to slow the progression of multiple sclerosis (MS), Alzheimer’s disease, and other similar diseases, according to 2 independent teams of researchers from the Washington University School of Medicine in St. Louis.
The waste that builds up on the brain is a byproduct of normal daily mental activities, explained a press release from the school. It is also a result of misdirected immune system attacks on brain cells. Neurologic disease can progress in this way if too much debris buildup is present in the brain for too long.
In the first study, published in the journal Cell, researchers aimed to address the basis for this genetic association in mice models. The researchers monitored the buildup of amyloid beta, which forms plaques in the brain, as the mice age to see if the absence of the TREM2 gene significantly accelerated the buildup. They were able to determine that in mice with the defective version of the TREM2 protein, Alzheimer’s disease brain plaques build up more slowly.
“We found that microglia cluster around amyloid plaques when TREM2 is present, presumably because the cells are getting ready to absorb the plaques and break them down,” first study author Marco Colonna, MD, continued in the statement. “When TREM2 is absent, this clustering does not occur.”
The second study, published in Acta Neuropathologica, found that mice lacking the same TREM2 protein had difficulty in clearing debris in the brain produced by damage to a protective coating on the nerve cells. The researchers administered a compound called cuprizone (which causes a loss of myelin, similar to human MS patients) to the mice that were bred to lack the TREM2 gene. After cuprizone exposure, motor coordination in the mice was impaired, too.
“We’ve been very interested in identifying ways to control naturally occurring mechanisms that help clean and repair the brain, and these new studies provide clear evidence that TREM2 could be just such a target,” said Laura Piccio, MD, PhD, assistant professor of neurology and senior author the second study. “When we give normal mice this chemical, they can clear most of the myelin fragments from the brain. But when we gave cuprizone to mice that did not have the gene and looked at their brains 4, 6, and 12 weeks later, we could still see evidence of damaged myelin.”
Both teams of researchers agree that the TREM2 protein may help keep microglia from self destruction as the debris is cleared from the brain.
“This is a mechanism that is very common in immune cells,” concluded Colonna. “When a signal activates immune cells and they start attacking an invader or working to repair an injury, they start using energy very rapidly. If the cells do not receive a second signal confirming the need for their services, this increased energy usage will kill them.”