Common Genetic Variant May Age The Brain

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via Medical News Today : Common genetic variant may age the brain

Researchers have identified a common genetic variant that disrupts normal brain aging and may increase susceptibility to Alzheimer’s disease and other neurodegenerative conditions.

In a new study, researchers found that older adults who possessed two “bad” copies of the gene TMEM106B showed greater aging in the frontal cortex – the brain region associated with higher cognitive functions – than those with two normal copies of the gene.

Study co-leader Herve Rhinn, Ph.D. – assistant professor of pathology and cell biology in the Taub Institute for Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center (CUMC) – and colleagues say that their study suggests that TMEM106B could be a biomarker for brain aging, and the gene could even be a target for new drugs for neurodegenerative diseases.

The team’s findings were recently published in the journal Cell Systems.

A number of studies have pinpointed specific genes that play a role in neurodegenerative diseases. One that has attracted much attention is apolipoprotein E (APOE), which has been associated with increased risk of Alzheimer’s disease.

However, according to Rhinn, these genes only play a small role. “By far, the major risk factor for neurodegenerative disease is aging. Something changes in the brain as you age that makes you more susceptible to brain disease,” he says. “That got us thinking, ‘What, on a genetic level, is driving healthy brain aging?'”

Biological vs. chronological brain age

To help answer this question, Rhinn and colleagues analyzed the autopsied brain tissue of 1,904 individuals who had been free of neurodegenerative disease.

The researchers looked at the transcriptome – the range of messenger RNA molecules initially produced by gene expression – of each tissue sample, which allowed them to determine the subjects’ brain biology at different ages.

The team then compared the transcriptome of each person’s brain tissue sample with the average transcriptome of age-matched individuals, searching for around 100 genes whose expression rises or falls with age.

As a result, the researchers were able to determine the difference between the biological age and chronological age of a person’s frontal cortex.

Biological age refers to an estimated age based on appearance, while chronological age refers the actual age.

Next, the team analyzed the genome of each subject, with the aim of identifying genetic variants that were associated with differences in biological and chronological age.

Bad TMEM106B variants may age frontal cortex by 12 years

From their analysis, the researchers found that variants of the gene TMEM106B – present in around two thirds of the general population – play a significant role in brain aging.

According to Rhinn and colleagues, around a third of the general population possess two copies of TMEM106B, while another third possess one copy.

They explain that up until the age of 65, the gene does not appear to influence brain aging.

“Until then, everybody’s in the same boat, and then there’s some yet-to-be-defined stress that kicks in,” says study co-leader Asa Abeliovich, Ph.D., professor of pathology and neurology in the Taub Institute. “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.”

In detail, the researchers found that older adults who possessed two bad copies of TMEM106B had a frontal cortex that was biologically 12 years older than that of individuals who had two normal copies of the gene.

The study revealed another variant in the progranulin gene that also appears to be involved in brain aging, but the team notes that the effects of this variant were not as strong as TMEM106B variants.

While the researchers cannot pinpoint the role these genetic variants play in neurodegenerative diseases – since the research looked at healthy brain tissue – the study does shed some light on the possible underlying processes.

“[…] it’s in healthy tissue that you start to get disease. It appears that if you have these genetic variants, brain aging accelerates and that increases vulnerability to brain disease. And vice versa: if you have brain disease, the disease accelerates brain aging. It’s a vicious cycle.” – Asa Abeliovich, Ph.D.

Further studies are needed, but the researchers believe that their findings could pave the way for strategies to prevent and treat neurodegenerative diseases.

Source : Medical News Today | Common genetic variant may age the brain

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