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A Gene that Preserves Brain Cells

Three senior women talk while seated at a table with a laptop and mugs of tea

As we age, our brains normally lose some cells. The amount of loss varies considerably, even in cognitively healthy persons, and genetic factors have been linked to higher risks of age-related losses. But do any genes protect the aging brain?

Yes, say researchers from the University of Minnesota and the Minneapolis VA Health Care System. They report that one form, or allele, of a particular gene protects a person from age-related reductions in the volume of gray matter. The allele—called  DRB1*13:02—is one of many in the Human Leukocyte Antigen, a large complex of genes that help our bodies defend against potentially harmful foreign matter.

Their study provides a basis for developing a drug or other treatment to mimic the function of the protective allele.

In various studies, this allele has been found to be protective against several viral and autoimmune diseases.

“Individuals who carry this allele derive significant protection from many conditions that affect the brain,” said study author Lisa James, Ph.D., Kunin Professor of Women’s Healthy Aging in the Department of Neuroscience and researcher at the Brain Sciences Center of the Minneapolis VA. “We [previously] found a similar protection against brain atrophy in Gulf War veterans who carried this allele.

“This gene is one of many factors, including diet and exercise, that help maintain brain function throughout the lifespan.”

The report is published in the journal EBioMedicine.

Personal Brain Drain

Research from many laboratories has shown that atrophy during normal aging claims between 2 and 5 percent of brain tissue per decade.

“So-called ‘healthy brain aging’ is a misnomer. Nothing is ‘healthy’ about it,” said Regents Professor of Neuroscience Apostolos Georgopoulos, Ph.D., MD, a study author and director of the Brain Sciences Center. “Our findings suggest that, instead, detrimental changes in the brain during aging may well be due to the persistent presence of brain-damaging substances that literally ‘chip the brain away.’”

Normal losses contrast sharply to conditions like Alzheimer's disease, where brain volumes shrink between 20 and 30 percent per decade.

Also, the losses are distributed unequally. The uppermost layer of the cerebrum—the cortex, or cortical area—is more prone to loss in the forward regions than posterior ones. And some lower, or subcortical, regions—like the hippocampus, amygdala and cerebellum—are susceptible while others, such as the brainstem, show hardly any loss.

Relative Ravages of Time

In the current study, the researchers studied 71 cognitively healthy women aged 32 to 69 years. Of those, 11 carried the protective allele and 60 did not.

The researchers used MRI imaging to measure each individual's gray matter. They assessed the total volume, as well as volumes of cortical and subcortical gray matter, and plotted the results against age.

The group lacking the protective allele showed a "highly statistically significant" reduction in total gray matter volume with age; it amounted to a loss of 4.2 percent of the mean volume per decade. Those with the protective allele showed no statistically significant loss.

Likewise, those lacking the allele showed statistically significant reductions in total cortical (4.7 percent) and subcortical (3.8 percent) mean gray matter volumes per decade, while those with the allele showed no statistically significant loss in either area.

Why and What Now

Many genes come in more than one allele, the result of DNA mutations in the past. The allele under investigation is one of many that code for proteins that are active in cells of the human immune system. The proteins help rid the body of harmful substances by attaching to them and stimulating the immune system to produce antibodies against them.

The researchers hypothesize that the protein made by the protective allele is essential for the production of antibodies that help eliminate substances that could otherwise cause brain inflammation and, ultimately, atrophy.

“Those fortunate people that carry the immunity genes that help eliminate those substances are literally ‘immune’ to age-related brain damage,” said Georgopoulos. “This gives hope for successful interventions to slow down or eliminate such brain damage and keep our most precious organ in good health.”

Deane Morrison

Deane Morrison

Deane is a writer and editor for University Relations. She also writes the Minnesota Starwatch column for the Minnesota Institute for Astrophysics.

morri029@umn.edu

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