COVID-19 and Alzheimer’s disease share the same genetic risk factor

LONDON — The same genetic risk factor which increases a person’s risk of developing Alzheimer’s disease may also make them more vulnerable to severe symptoms of COVID-19, a new study warns. Researchers at University College London have discovered that variants of the OAS1 gene play a role in both increasing dementia risk and worse coronavirus infections.

Specifically, a variant of the OAS1 gene can increase a person’s risk of developing Alzheimer’s by three to six percent. The study finds OAS1 variants also raise the odds of needing intensive care for COVID-19 by up to 20 percent. The discovery may open the door to treatments for both conditions.

“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. We have found that some of the same immune system changes can occur in both Alzheimer’s disease and COVID-19,” says lead author Dr. Dervis Salih in a university release.

“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.”

The link between the immune system and brain cells

Researchers say the OAS1 gene is expressed in microglia, which are immune cells that make up about 10 percent of all the cells in the brain. The team sequenced genetic data from 2,547 people during the study. Half of these individuals had Alzheimer’s disease, the most common form of dementia.

Results show one particular variant in the OAS1 gene, rs1131454, makes someone 11 to 22 percent more likely to develop Alzheimer’s. Scientists say this variant in the anti-viral gene is extremely common, with over half of Europeans carrying it.

While investigating four other variants of this gene, which all dampen its activity, the team found that variants increasing Alzheimer’s risk also appear to increase the risk of experiencing severe symptoms of COVID-19.

What does OAS1 do?

The study finds this gene controls the amount of pro-inflammatory proteins the body’s immune cells release. Researchers treated microglia cells to mimic the impact of a COVID infection. In cells that expressed the OAS1 gene with less potency, the cells had an “exaggerated response” to the illness.

This overreaction produced what scientists call the “cytokine storm” — where the immune system releases too many inflammatory agents to battle disease. The result sees a person’s own immune system attack healthy tissues in the body, leading to potentially life-threatening complications.

One problem with OAS1 activity is that it changes with age, which could be why older people are more at risk for both Alzheimer’s and COVID.

“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,” says PhD student Naciye Magusali from the UK Dementia Research Institute at UCL.

“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,” Dr. Salih adds.

The study appears in the journal Brain.