Genetic link between alcoholism and Alzheimer’s risk discovered
Scientists have found a genetic overlap between alcohol use disorder (AUD) and neurodegenerative disorders such as Alzheimer’s.
In a study published in Nature Communications, the researchers identified several genes associated with alcoholism, including two previously linked to neurodegenerative disorders.
First of its kind study using multi-omics approach identifies large list of candidate genes associated with alcohol use disorder - study shows potential genetic link between #alcoholism, #Alzheimers disease, & other neurodegenerative disorders https://t.co/kzautcL6DN#genetics pic.twitter.com/nUNbvYf2L8
— Mount Sinai Genetics (@SinaiGenetics) August 20, 2021
“Several of these genes are also associated with neurodegenerative disorders - an intriguing connection because of alcohol’s ability to prematurely age the brain,” David Goldman, a neurogenetics researcher at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) told The Scientist.
The scientists compared the genetic data of about 700,000 families involved in the NIAAA’s Collaborative Studies on the Genetics of Alcoholism (COGA), as well as data from the UK Biobank, against analyses of adult and foetal brains to determine which genes were silenced or expressed.
Though the study did identify many genes associated with alcohol use, the team focused on the two genes linked to neurodegenerative disorders: SPI1 and MAPT.
SPI1 produces a protein that controls the activity of immune cells, while MAPT produces a protein found throughout the nervous system called tau.
SPI1 linked to Alzheimer’s
Previous research has shown that SPI1 influenced the likelihood of a person developing Alzheimer’s disease, with some theorising that it influences the activity of microglia, immune cells that are found in the brain.
In a study from two years ago, Manav Kapoor, a neuroscientist and geneticist at the Icahn School of Medicine at Mount Sinai and the new paper’s first author, and his team found evidence that people with AUD might have an overactive immune system - and this new paper could help explain their previous findings.
The new study also found an association between the SPI1 gene and both heavy drinking and a diagnosis of AUD.
Though alcoholism is already associated with immune dysfunction, the team found that expression of the SPI1 gene was higher in some foetal brains.
Kapoor says this finding suggests that those genetically predisposed to AUD and heavy drinking are also predisposed to developing an overactive immune system.
If this is the case, when people with particular versions of the gene drink heavily, Kapoor suggests that their immune systems could become overactivated and cause brain immune cells to alter connections between neurons.
Kapoor bases this theory on a previous study in mice that found that binge drinking activated brain immune cells, which selectively pruned certain synapses and caused the animals to display anxiety-like behaviours.
The activation of these brain immune cells could result in the pruning of connections to neurons that produce dopamine - the chemical behind the “reward” feeling we get after drinking alcohol.
As a result, people with certain versions of SPI1 who start drinking regularly would “have to drink more and more to get the same level of reward”, Kapoor says.
“And their immune system will get more activated”, pruning more synapses.
“It will become a vicious cycle,” Kapoor says.
As for MAPT, the gene isn’t associated with AUD, but is associated with consuming more drinks per week.
The tau protein it produces is thought to play a major role in neurodegenerative disorders including Alzheimer’s, Parkinson’s, frontotemporal dementia, and supranuclear palsy.
However, it is still unclear how tau may factor into the consumption of alcohol.
Why this matters
Joel Gelernter, a geneticist and neurobiologist at Yale University School of Medicine, who was not involved in the study, says the study is “a really necessary step in unravelling the biology of alcohol intake and alcohol use disorder”.
Kapoor says this work could benefit people in a few ways.
First, he believes that drugs currently in development to treat neurodegenerative disorders could be repurposed to help people in reducing or stopping drinking.
Second, it could be a way of reducing a person’s risk for neurodegenerative disorders.
“If we can identify some group of people that are more at risk of Alzheimer’s disease, we can ask them to reduce their drinking,” he says.
“That might be beneficial to them.”
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