Tue. May 17th, 2022

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An antiviral gene that affects the risk of both Alzheimer’s disease and severe COVID-19 has been identified by a UCL-led research team.

The researchers estimate that a genetic variant of OAS1 gene increases the risk of Alzheimer’s disease by about 3-6% in the population as a whole, while related variants of the same gene increase the likelihood of severe COVID-19 outcomes.

The results, published in Brain, could open the door to new drug development goals or track disease progression in both diseases and suggest that developed treatments could be used for both conditions. The results also have potential benefits for other related infectious conditions and dementia.

Main author Dr. Dervis Salih (UCL Queen Square Institute of Neurology and UK Dementia Research Institute at UCL) said: “While Alzheimer’s is primarily characterized by harmful amyloid protein buildup and entanglements in the brain, there is also widespread inflammation in the brain that highlights the importance of the immune system for 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 may also be inflammatory changes in the brain. Here, we have identified a gene that may contribute to an excessive immune response to increase the risk of both Alzheimer’s and COVID-19.”

For the study, the research team tried to build on their previous work, which found evidence from a large data set of human genomes, to suggest a link between OAS1 gene and Alzheimer’s disease.

That OAS1 gene is expressed in microglia, a type of immune cell that makes up about 10% of all cells found in the brain. By further examining the gene’s link to Alzheimer’s, they further sequenced the genetic data from 2,547 people, half of whom had Alzheimer’s disease. They found that humans with a particular variation, called rs1131454, of 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 was identified is common as well over half of Europeans are thought to carry it and it has a greater impact on Alzheimer’s risk than several known risk genes.

Their findings add OAS1, an antiviral gene, to a list of dozens of genes now known to affect a person’s risk of developing Alzheimer’s disease.

The researchers examined four variants of OAS1 gene, all of which inhibit its expression (activity). They found that the variants that increase the risk of Alzheimer’s disease are linked (inherited) to OAS1 variants have recently been shown to increase the baseline risk of needing intensive treatment for COVID-19 by as much as 20%.

As part of the same research, researchers in immune cells treated to mimic the effects of COVID-19 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 excessive response to tissue damage, releasing what they call a ‘cytokine storm’, leading to an autoimmune condition in which the body attacks itself.

OAS1 activity changes with age, so further research into the genetic network can help understand why older people are more vulnerable to Alzheimer’s, COVID-19 and other related diseases.

Ph.d. student Naciye Magusali (UK Dementia Research Institute at UCL) said: “Our results suggest that some people may have an increased susceptibility to both Alzheimer’s disease and severe COVID-19, regardless of their age, as some of our immune cells appear to engage a common molecular mechanism in both diseases. “

Following the outbreak of the COVID-19 pandemic, researchers from the UK Dementia Research Institute at UCL have focused their attention on investigating the long-term neurological consequences of the virus. Using biomarkers found in the blood and fluid around the central nervous system, they aim to detect neuroinflammation and damage to the neurons.

Dr. Salih said: “If we could develop a simple way to test these genetic variants when someone tests positive for COVID-19, it may be possible to identify who is at greater risk of needing critical care, but there are lots of more work to get us in. Similarly, we hope our research can feed the development of a blood test to identify if anyone is at risk of developing Alzheimer’s before they show memory problems.

“We also continue to investigate what happens when this immune network has been activated in response to an infection such as COVID-19, to see if it leads to lasting effects or vulnerabilities, or if we understand the brain’s immune response to COVID. 19, involves OAS1 gene, may help explain some of the neurological effects of COVID-19. ”


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More information:
A genetic link between the risk of Alzheimer’s disease and severe COVID-19 results via the OAS1 gene, Brain (2021). DOI: 10.1093 / brain / awab337

Journal information:
Brain

Provided by University College London

Citation: Alzheimer’s and COVID-19 share a genetic risk factor (2021, October 8) retrieved October 8, 2021 from https://medicalxpress.com/news/2021-10-alzheimer-covid-genetic-factor.html

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