Researchers have identified a genetic link between Alzheimer’s and severe cases of COVID-19 that may open new avenues into the treatment of both diseases.
The study, published in the journal Brain, found that the presence of a variant of the OAS1 gene increases the risk of developing Alzheimer’s disease by three to six per cent, while similar variants of the same gene increase the odds of contracting a case of severe COVID. In addition to presenting new possibilities for treatment, researchers hope this overlap may shed light on other infectious diseases and dementias.
“While Alzheimer’s is primarily characterized 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 Dervis Salih, lead author of the study from the UCL Queen Square Institute of Neurology and the U.K. Dementia Research Institute at UCL. “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.”
Alzheimer’s disease, the most common cause of dementia, is a degenerative condition that is believed to be the result of the accumulation of certain proteins in the brain that leads to the slow death of neurons. This process eventually produces symptoms of memory loss, difficulty thinking or problem solving and changes in mood and behaviour. There are over 500,000 Canadians living with dementia today, with another 25,000 diagnosed with the progressive disease every year, according to the Alzheimer Society. Two-thirds of those diagnosed over the age of 65 are women. With the rate at which the disease is growing, it costs over $12-billion a year to care for patients.
As COVID-19 quickly circled the globe, researchers noticed that some of the symptoms of infection — particularly the enduring brain fog associated with cases of long COVID — bore striking similarities to the experiences of Alzheimer’s patients. Previous work by the current researchers uncovered a link between the degenerative disease and the OAS1 gene, which is expressed in microglia, a type of immune cell that makes up about 10 per cent of all cells found in the brain.
Further investigation revealed that a variation of this gene, called rs1131454, increased a carrier’s baseline risk of Alzheimer’s disease by 11 to 22 per cent. Around half of all Europeans are believed to carry this variant, making its impact on the disease likely greater than other genes known to contain similar risks.
The team investigated four variants of OAS1 and found that in addition to dampening the activity of the gene and increasing the risk of Alzheimer’s, the variants were linked — or inherited together — and raised the risk of severe COVID by as much as 20 per cent.
They also found that the OAS1 gene exerts control over amount of pro-inflammatory proteins the immune system releases. Microglia cells that expressed the gene more weakly were more likely to overreact to tissue damage and create a cytokine storm that caused the body’s immune system to attack itself. Because the activity of this gene accelerates with age, subsequent research may be able to unlock why older individuals are more prone to Alzheimer’s, severe COVID and other similar diseases.
“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,” said Naciye Magusali, a PhD student at UK Dementia Research Institute at UCL.
The researchers, who normally study dementia, have turned their attention to the long-term neurological effects of COVID, tracking neuroinflammation and neuron damage in the hopes of shedding new light on both diseases. “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,” Salih said. “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.”
Dave Yasvinski is a writer with Healthing.ca