MAR 03, 2015 04:04 PM PST

New Target Identified in Fight Against Alzheimer's, Multiple Sclerosis

Highlighting a potential target in the treatment of multiple sclerosis (MS) and Alzheimer's disease, new research suggests that triggering a protein found on the surface of brain cells may help slow the progression of these and other neurological diseases.

Protein may help to treat neurological disorders

Working with mice, two research teams at Washington University School of Medicine in St. Louis independently linked the protein to the ability to clear debris from the brain. Such waste builds up both as a byproduct of daily mental activities and as a result of misdirected immune system attacks on brain cells. If too much debris is present in the brain for too long, it can contribute to neurological disease.

In one study, appearing online Feb. 26 in Cell, scientists showed that Alzheimer's brain plaques build up more slowly in mice that have a defective version of the TREM2 protein. In another, published Jan. 29 in Acta Neuropathologica, researchers showed that mice lacking the same protein had trouble cleaning up debris in the brain produced by damage to a protective coating on nerve cells. The problem is thought to occur in MS and other neurological disorders.

"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 of one of the studies.

Scientists are looking for ways to activate the protein to slow or prevent damage caused by neurological disorders.

Previous studies have 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 (ALS).

Scientists knew the protein was found on brain cells called microglia, which help maintain and repair the central nervous system. The new studies are among the first to provide clear evidence that the protein plays an integral role in at least some of these processes.

In Alzheimer's disease, amyloid beta, a byproduct of brain metabolism that is normally cleared from the brain, builds up to form plaques. Researchers in the laboratories of Marco Colonna, MD, the Robert Rock Belliveau MD Professor of Pathology, and John Cirrito, PhD, associate professor of neurology, bred mice lacking the gene with mice genetically engineered to have an Alzheimer's-like condition.

First author Yaming Wang, PhD, a postdoctoral research scholar, monitored the buildup of amyloid plaques in the mice offspring as they aged and found that the absence of the gene significantly accelerated the accumulation of the plaques.

"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 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. Failure to promptly remove this debris can worsen damage caused by the condition and inhibit repair mechanisms.

For the MS study, Piccio and colleagues at the John L. Trotter MS Center at Washington University School of Medicine and Barnes-Jewish Hospital gave a compound called cuprizone to mice that lacked the TREM2 gene. Cuprizone causes loss of myelin in a manner somewhat similar to that seen in people with MS.

"When we give normal mice this chemical, they can clear most of the myelin fragments from the brain," Piccio said. "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."

Motor coordination in these mice also was significantly more impaired after cuprizone exposure. This may reflect enhanced damage to brain cells resulting from the lingering presence of damaged myelin in the brain.

Colonna and his colleagues showed that TREM2 detects molecules associated with amyloid beta and with damaged neurons. They believe that the protein helps keep microglia from self-destructing as debris is cleared from the brain.

"This is a mechanism that is very common in immune cells," he explained. "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."

Source: Washington University School of Medicine
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
You May Also Like
SEP 04, 2018
Drug Discovery
SEP 04, 2018
Dopamine Provided Targeted Therapy for Neuropsychiatric Disorders
According to a study published in Molecular Psychiatry, research scientists at Columbia University Vagelos College of Physicians and Surgeons have brought ...
SEP 05, 2018
Neuroscience
SEP 05, 2018
New Research on How the Brain Learns
Understanding how the brain learns is a complex undertaking. There are billions of neurons in the mind that signal each other furiously every day. Memories...
OCT 30, 2018
Cannabis Sciences
OCT 30, 2018
Marijuana Withdrawal Syndrome
The perception of marijuana's safety is prevalent among chronic users. Dr. Samuel Wilkinson and colleagues from the Department of Psychiatry at Ya...
NOV 03, 2018
Technology
NOV 03, 2018
Neurotechnology Treats Paralysis
The latest study at the intersection of technology and neuroscience is the STIMO (STImulation Movement Overground) study, which has established the ne...
NOV 16, 2018
Genetics & Genomics
NOV 16, 2018
Using Light to Control Organ Development
Optogenetics combined genetic engineering with optics to create a way to control cellular behaviors with light....
NOV 19, 2018
Plants & Animals
NOV 19, 2018
Communal Rearing Better Prepares Mice for the Real World, Study Finds
Researchers have long understood early-life experiences to influence actions and behavior later in life for humans, but can be same be said about animals?...
Loading Comments...