Missing link between severe COVID-19 and Alzheimer’s disease discovered
Early in the pandemic researchers saw disproportionately high rates of dementia patients suffering from severe COVID-19. A common hypothesis was that memory impairments associated with neurodegeneration affect a person’s ability to consistently follow infection control measures such as social distancing and mask wearing. But a new study led by scientists from University College London is proposing a key gene variant, known to heighten one’s risk for Alzheimer’s, stimulates the body’s inflammatory responses and can lead to greater susceptibility to severe COVID-19.
In 2019 a team of researchers discovered a handful of genes that could be associated with heightened risk of Alzheimer’s disease. A separate study last year found variants in one of these Alzheimer’s risk genes, OAS1, correlated with severe COVID-19 outcomes.
This new study, published in the journal Brain, proposes OAS1 regulates the inflammatory responses of certain cells. And some OAS1 variants dampen that regulatory response leading to pro-inflammatory activity, which can explain how it both heightens Alzheimer’s risk and severe COVID-19.
“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,” says lead author Dervis Salih. “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.”
Homing in on one particular OAS1 variant, dubbed rs1131454, the research first confirmed the variant can increase a person’s baseline risk of developing Alzheimer’s disease by up to 22 percent. This variant is thought to be extremely common, carried by over 50 percent of Europeans.
Studying the molecular mechanisms of this OAS1 variant the researchers discovered it can lead to overactive inflammatory responses, and it is this action that plays a role in the progression of severe COVID-19. David Strain, a researcher from the University of Exeter, calls the new study “robust” and suggests the findings fit with what we know of the "cytokine storms" that are part of the severe stages of COVID-19.
“We do know that one of the key pathways in development of Alzheimer’s disease is inflammation within the brain tissue, and, as our understanding of the pandemic has grown, we have seen many other inflammatory conditions be highlighted as risk factors for poor outcomes, therefore the results are not overly surprising,” says Strain, who did not work on the this new research.
Of course, these new findings do raise a whole heap of new questions. Salih indicates the UCL research team are now looking at what role this gene variant could be playing in long COVID, or how it could be influencing some of the more acute neurological symptoms that can be associated with the disease.
“We are also continuing to research what happens once this immune network has been activated in response to an infection like Covid-19,” says Salih, “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.”
Perhaps a more immediate outcome from these new findings could be a way to easily detect those patients most at risk of severe COVID-19. Salih even speculates a simple blood test identifying this particular genetic variant could serve as a way to identify early Alzheimer’s patients.
“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,” says 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.”
The new study was published in the journal Brain.
Source: University College London