Genetic variant increases Alzheimer's and severe COVID-19 risk

A gene variant has been identified that is linked to the development of both Alzheimer's and severe COVID-19, new research has found.

Possessing a variant of the OAS1 gene with a single nucleotide polymorphism was found to lead to significant downregulation of the gene in a type of brain cell (microglia) of both individuals with Alzheimer's and those with severe presentation of COVID-19. The OAS1 gene is associated with an enzyme that breaks down RNA of viral and host cells as part of an immune response to viruses. Carrying this gene variant was linked to as much as a 22 percent increased risk in developing Alzheimer's while also associated with as much as a 20 percent greater probability of needing intensive care for COVID-19.

'Fairly early in the pandemic, people with dementia emerged as a group at particular risk of severe COVID-19 infection. While there are likely to be several reasons for this, the study raises the possibility of a shared genetic risk factor playing a role' said Dr Rosa Sancho, head of research at Alzheimer's Research UK, a researcher not involved in the study.

Over half of Europeans possess this identified gene variant which is linked to the molecular pathways responsible for the release of inflammatory biomarkers, called cytokines, within the brain leading to the damage of neurons. Researchers spearheaded by the UK Dementia Research Institute at University College London (UCL), analysed the genetic sequences of 2547 people, 1313 of whom had Alzheimer's disease and found that many of those with Alzheimer's disease had the implicated gene variant. In addition, single-cell RNA sequencing showed expression of the mouse equivalent of the gene variant increased with age.

This discovery follows on from research conducted by the University of Glasgow, highlighting another OAS1 gene variant that protects carriers by eliciting an earlier immune response after SARS-Cov-2 infection, the virus which leads to COVID-19 (see BioNews 1115). The researchers aim to further these findings by tracking the inflammatory biomarkers in the blood and other bodily fluids around the central nervous system to better assess the damage COVID-19 has on the brain.

'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' said Dr Dervis Salih, a lead author and researcher at the UK Dementia Research Institute at UCL.