US Pharm. 2022;47(1):1.

Researchers from University College London (UCL) and several other universities in the UK estimate that one genetic variant of the OAS1 gene increases the risk of Alzheimer’s disease (AD) by about 3% to 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 could be used for both conditions. The findings also have potential benefits for other related infectious conditions and dementias.

Lead author Dervis Salih of UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL said, “While Alzheimer’s is primarily characterized by harmful buildup 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.”

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 AD. 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 AD further, they sequenced genetic data from 2,547 people, half of whom had AD. They found that people with a particular variation, called rs1131454, of the OAS1 gene were more likely to have AD, increasing carriers’ baseline risk of AD by an estimated 11% to 22%.

The researchers investigated four variants on the OAS1 gene, all of which dampen its expression (activity). They found that the variants increasing the risk of AD are linked (inherited together) with OAS1 variants recently found to increase the baseline risk of needing intensive care for COVID-19 by as much as 20%.

As part of the same research, 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 proinflammatory 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.

Dr. Salih said, “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. 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.”

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