Discovery unveils genetic risk factor shared by Alzheimer’s and COVID-19

Scientists have identified the OAS1 gene as a risk factor for both Alzheimer’s disease and COVID-19, suggesting potential drug targets.

Brain highlighted in orange surrounded my COVID-19 cells

A new study conducted at University College London (UCL), UK, has revealed an antiviral gene that impacts the risk of both Alzheimer’s disease and severe COVID-19. According to the researchers, the findings could pave the way for new drug targets that could treat both conditions.

The team estimate that one genetic variant of the OAS1 gene increases the risk of Alzheimer’s disease by about three to six percent in the population as a whole, while related variants on the same gene increase the likelihood of severe COVID-19 outcomes.

“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. We have found that some of the same immune system changes can occur in both Alzheimer’s disease and COVID-19,” explained lead author Dr Dervis Salih. “In patients with severe COVID-19 infection there can also be inflammatory changes in the brain. Here we have identified a gene that can contribute to an exaggerated immune response to increase risks of both Alzheimer’s and COVID-19.”

Investigating the gene’s link to Alzheimer’s further, the researchers sequenced genetic data from 2,547 people, half of whom had Alzheimer’s disease. They found that people with a variation called rs1131454 of the OAS1 gene were more likely to have Alzheimer’s disease, increasing carriers’ baseline risk of Alzheimer’s by an estimated 11 to 22 percent. The new variant identified is common and it has a bigger impact on Alzheimer’s risk than several known risk genes.

The researchers then investigated four variants on the OAS1 gene, all of which dampen its expression. They discovered that the variants increasing the risk of Alzheimer’s disease are linked with OAS1variants recently found to increase the baseline risk of needing intensive care for COVID-19 by as much as 20 percent.

As part of the same research, published in Brain, the team found that the gene controls how much the body’s immune cells release pro-inflammatory proteins in immune cells treated to mimic the effects of COVID-19. They found that microglia cells where the gene was expressed more weakly had an exaggerated response to tissue damage, unleashing a ‘cytokine storm’ that leads to an autoimmune state where the body attacks itself. According to the team, 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.

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“If we could develop a simple way of testing for these genetic variants when someone tests positive for COVID-19, then it might be possible to identify who is at greater risk of needing critical care, but there is plenty more work to be done to get us there,” continued Salih. “Similarly, we hope that our research could feed into the development of a blood test to identify whether someone is at risk of developing Alzheimer’s before they show memory problems.

“We are also continuing to research what happens once this immune network has been activated in response to an infection like COVID-19, to see whether it leads to any lasting effects or vulnerabilities, or if understanding the brain’s immune response to COVID-19, involving the OAS1 gene, may help to explain some of the neurological effects of COVID-19,” Salih added.