Brain aging linked to common genetic variant

An MRI scan of an Alzheimer's patient's brain
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A group of researchers has discovered a genetic variant that appears to have a significant impact on how quickly the brain ages in older people, and that may influence a person's risk of developing neurodegenerative diseases.

The research was reported Wednesday in the journal Cell Systems.

"If you look at a group of seniors, some will look older than their peers and some will look younger," said the study's co-author Asa Abeliovich in a news release. "The same differences in aging can be seen in the frontal cortex, the brain region responsible for higher mental processes."

The researchers found that these differences can be traced to the presence of mutated or damaged copies of a gene called TMEM106B. "A person with two 'bad' copies of this gene have a frontal cortex that, by various biological measures, appears 12 years older than those who have two normal copies," added Abeliovich, who is a professor of pathology and neurology at Columbia University Medical Center.

The team made the discovery by examining genetic information from brain samples taken from 1,904 deceased people without neurodegenerative disease. It then performed a genome-wide association study, meaning it looked for specific genetic variations that were associated with increases in biological aging among people who were the same chronological age.

"TMEM106B begins to exert its effect once people reach age 65," said Dr. Abeliovich. "Until then, everybody's in the same boat, and then there's some yet-to-be-defined stress that kicks in. If you have two good copies of the gene, you respond well to that stress. If you have two bad copies, your brain ages quickly."

Because the tissues the team studied all came from people free of brain disease, the researchers said their findings do not establish a link between the genetic variant and neurodegenerative disease. However, only that the gene appears to play a big role in accelerated brain aging, and aging in turn could make a brain more vulnerable to the stresses of disease.

"By far, the major risk factor for neurodegenerative disease is aging," said study co-author Herve Rhinn, an assistant professor of pathology and cell biology at Columbia University Medical Center, in the release. "Something changes in the brain as you age that makes you more susceptible to brain disease. That got us thinking, 'What, on a genetic level, is driving healthy brain aging?'"

The research was funded by the National Institute on Aging, the Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke.

Both researchers are consultants to San Francisco–based biotech firm Alector, which develops therapies for dementia and other neurodegenerative diseases. Abeliovich is one of Alector's co-founders.