London, October 8
Scientists have identified a gene that impacts the risk of both Alzheimer’s disease and severe COVID-19, a finding that could pave the way for new targets for drug development for both the diseases.
The researchers estimate that one genetic variant of the OAS1gene increases the risk of Alzheimer’s disease by about 3-6 per cent in the population as a whole, while related variants on the same gene increase the likelihood of severe COVID-19 outcomes.
The findings, published in the journal Brain, could open the door for new targets for drug development or tracking disease progression in either disease.
The findings also have potential benefits for other related infectious conditions and dementias, according to the researchers.
“While Alzheimer’s is primarily characterised by harmful build-up of amyloid protein and tangles in the brain, there is also extensive inflammation in the brain that highlights the importance of the immune system in Alzheimer’s,” said study lead author Dervis Salih from University College London (UCL) in the UK.
“We have found that some of the same immune system changes can occur in both Alzheimer’s disease and COVID-19,” Salih said.
In patients with severe COVID-19 infection there can also be inflammatory changes in the brain, the researchers said.
The newly identified gene can contribute to an exaggerated immune response to increase risks of both Alzheimer’s and COVID-19, they said.
The OAS1 gene is expressed in microglia, a type of immune cell that constitutes around 10 per cent of all cells found within the brain.
The researchers sequenced genetic data from 2,547 people, half of whom had Alzheimer’s disease.
They found that people with a particular variation, called rs1131454, of the OAS1 gene were more likely to have Alzheimer’s, increasing carriers’ risk of the disease by an estimated 11-22 per cent.
Their findings add OAS1, an anti-viral gene, to a list of dozens of genes now known to affect a person’s risk of developing Alzheimer’s disease.
The researchers investigated four variants on the OAS1 gene, all of which dampen its activity.
They found that the variants increasing the risk of Alzheimer’s disease are inherited together with OAS1 variants recently found to increase the risk of needing intensive care for COVID-19 by as much as 20 per cent.
In immune cells treated to mimic the effects of COVID-19, the researchers found that the gene controls how much the body’s immune cells release pro-inflammatory proteins.
They found that microglia cells where the gene was expressed more weakly had an exaggerated response to tissue damage, unleashing what they call a ‘cytokine storm,’ which leads to an autoimmune state where the body attacks itself.
OAS1 activity changes with age, so further research into the genetic network could help to understand why older people are more vulnerable to Alzheimer’s, COVID-19, and other related diseases, the researchers said.
“Our findings suggest that some people may have increased susceptibility to both Alzheimer’s disease and severe COVID-19, irrespective of their age, as some of our immune cells appear to engage a common molecular mechanism in both diseases,” UCL PhD student Naciye Magusali added. PTI
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