An anti-viral gene that increases the risk of both Alzheimer’s disease and severe Covid-19 has been identified by a UCL-led research team.
The researchers estimate that one genetic variant of the OAS1 gene increases the risk of Alzheimer’s disease by about 3-6% 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 Brain, could open the door for new targets for drug development or tracking disease progression in either disease, and suggest that treatments developed could be used for both conditions. The findings also have potential benefits for other related infectious conditions and dementias.
Lead author Dr Dervis Salih (UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL) said: “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.
“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.”
For the study the research team sought to build on their previous work, which found evidence from a large dataset of human genomes, to suggest a link between the OAS1 gene and Alzheimer’s disease.
The OAS1 gene is expressed in microglia, a type of immune cell that constitutes around 10% of all cells found within the brain. Investigating the gene’s link to Alzheimer’s further, they 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 disease, increasing carriers’ baseline risk of Alzheimer’s by an estimated 11-22%. The new variant identified is common, as just over half of Europeans are believed to carry it, and it has a bigger impact on Alzheimer’s risk than several known risk genes.
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.