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New protein target found in fight against Alzheimer's, MS

New protein target found in fight against Alzheimer's, MS
3rd March 2015

Triggering a protein on the surface of brain cells could help to slow the progression of Alzheimer's and Multiple Sclerosis (MS).

The protein, known as TREM2, was found to help cells known as microglia to clear up debris from the brain, eliminating one of the factors that can lead to the development of neurological disorders.

Working with mice, two research teams at Washington University School of Medicine in St. Louis made the discovery independently. 

Previous research has linked rare forms of the TREM2 gene to early-onset dementia and increased risk of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. 

The scientists bred mice lacking the gene with mice genetically engineered to have an Alzheimer's-like condition. They discovered that amyloid plaques formed more quickly in those that did not have the gene.

"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," said one of the researchers, Dr Marco Colonna. "When TREM2 is absent, this clustering does not occur."

In MS, misdirected immune cell attacks damage myelin, a protective coating on nerve cells, leaving myelin fragments in brain tissue. If this debris is not removed, damage caused by the condition can be worsened and repair mechanisms inhibited.

The MS study involved giving cuprizone, which causes loss of myelin, to mice that lacked the TREM2 gene. While myelin fragments were removed from the brains of the normal mice, they were present in the brains of the mice without the gene 12 weeks later.

TREM2 was shown to detect molecules associated with amyloid beta and damaged neurons. The scientists believe the protein helps keep microglia from self-destructing as debris is cleared from the brain.

Self-destruction is a common feature of immune cells. When they receive a signal, they use large amounts of energy to repel an invader or clear up damage. Unless they receive a second signal, this increased energy use kills the cells.

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