October 8, 2021

expert reaction to study of genetic link between risk for Alzheimer’s disease and severe COVID-19 outcomes

A study published in Brain looks at a genetic link between risk for Alzheimer’s disease and severe COVID-19 outcomes via the OAS1 gene.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“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.

“This molecular study highlights a mechanism by which this genetic risk factor leads to overactive inflammation, a process that can contribute to the progression of Alzheimer’s disease and worsen the symptoms of COVID-19.

“There is emerging evidence of neurological changes that may persist in some people who have contracted COVID-19, and researchers are working to understand how these might impact a person’s future health. We don’t know whether the effects of this risk gene could influence long-term neurological consequences of COVID-19 or whether COVID-19 infection increases the risk of dementia later in life.”

Dr David Strain, Senior Clinical Lecturer, University of Exeter, said:

“This is robust research that supports some of the early observations that people with Alzheimer’s disease were at an increased risk of poor outcomes from COVID-19. At first we thought that was because people with dementia were less likely to be able to adhere to physical distancing and mask wearing, or were exposed in their care institutions when there was a mass discharge from hospitals. However, even after adjustment for these risk factors, those with even early dementia were still at a much higher risk. 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. It does add important information as to the pathogenesis of the more severe presentations of COVID and will hopefully be able to shed further light on potential treatment options or even personalised preventative medicine.”

Dr Kenneth Baillie, Academic Consultant in Critical Care Medicine, Roslin Institute, University of Edinburgh, Chief Investigator, Genetics of Mortality in Critical Care Study (GenOMICC) and co-lead, ISARIC4C study, said:

“It’s great to see a great deal of research building on our discovery last year that OAS1 variants are associated with severe Covid-19. In the ISARIC4C study we recently found that this is probably due to a change in the way cell membranes detect viruses (Science, Sept 2021) but this mechanism doesn’t explain the fascinating association with Alzheimer’s disease reported in this new work. There are many possibilities to explain why this happens – it is often the case that the same gene can have different roles in different parts of the body. Importantly, it doesn’t mean that having Covid has any effect on your risk of Alzheimer’s.”

References:

GenOMICC study: https://www.nature.com/articles/s41586-020-03065-y

ISARIC4C report: https://www.science.org/doi/10.1126/science.abj3624

Prof Jonathan Schott, Professor of Neurology, University College London, said:

“Dementia is the main pre-existing health condition associated with COVID-19 mortality, accounting for ~1 in 4 deaths from COVID between March and June 2020. While some of this excessive mortality may relate to people with dementia being overrepresented in care homes which were particularly hard hit by the pandemic, or due to general increased vulnerability to infections, there have been questions as to whether there are common factors that might increase susceptibility both to developing dementia and to dying from COVID-19. In this elegant paper, Magusali and colleagues provide evidence for the latter, suggesting a common genetic mechanism both for Alzheimer’s disease and for severe COVID-19 infection. The identification of a genetic risk factor and elucidation of inflammatory pathways through which it may increase risk has important implications for our understanding of both diseases, with potential implications for novel treatments.”

‘A genetic link between risk for Alzheimer’s disease and severe COVID-19 outcomes via the OAS1 gene’ by Naciye Magusali et al was published in Brain at 00:01 UK time on Friday 8 October.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Dr Rosa Sancho: “This study was partly supported by Alzheimer’s Research UK funding.”

Prof Jonathan Schott: “Prof Schott is a UCL employee but also serves as Chief Medical Officer for ARUK and Clinical Advisor to UKDRI.”

None others received.