Protein shown to slow progress of Alzheimer’s and multiple sclerosis
Researchers have identified a promising new target in the battle against certain neurological diseases. A protein known as TREM2 has been proven effective in clearing away unwanted debris in the brain, the unchecked buildup of which can lead to both Alzheimer's disease and multiple sclerosis (MS).
Earlier research has suggested that variants of the TREM2 protein are related to neurological diseases, such as dementia, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Located in brain cells called microglia, the protein carries out the task of maintaining and repairing the body' central nervous system, leading researchers to think it could function as a trigger in treating such conditions.
Scientists at the Washington University School of Medicine in St Louis undertook two independent studies exploring the ability of the TREM2 protein to keep the brain free of debris.
The first investigated its ability to treat Alzheimer's. One of the contributing factors to the onset of this condition is the buildup of brain plaques, which are made up of proteins known as amyloid beta. These proteins are meant to be cleared away naturally, but when they are able to accumulate they can cause damage to the synapses and result in symptoms like memory loss.
The research team bred mice without the TREM2 gene with mice that were engineered to have an Alzheimer's-like condition. They then tracked the buildup of the amyloid beta proteins in the offspring and observed that the absence of the TREM2 gene greatly increased the rate of accumulation.
"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," says Marco Colonna, a Professor of Pathology at Washington University. "When TREM2 is absent, this clustering does not occur."
The second study was to explore the role of TREM2 in the onset of MS. A factor in the development of this disease is thought to be attacks by immune cells, mistakenly aimed at a protective layer on the nerve cells called myelin. This process sees fragments of myelin remain lodged in the brain tissue, compounding the effects of condition and impairing the ability of the brain to repair itself.
Working with mice who were missing the TREM2 gene, the scientists treated the rodents with cuprizone, a compound that mimics MS by creating a loss of myelin.
"When we give normal mice this chemical, they can clear most of the myelin fragments from the brain," says Laura Piccio, PhD assistant professor of neurology and senior author of one of the studies. "But when we gave cuprizone to mice that did not have the gene and looked at their brains four, six and 12 weeks later, we could still see evidence of damaged myelin."
The scientists are hopeful that the TREM2 protein might be manipulated in a way that halts the development of neurological disorders in humans.
"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," says Piccio, MD.