Editor’s Note: Find the latest COVID-19 news and guides at Medscape’s Coronavirus Resource Center.
Alzheimer’s disease (AD) risk and susceptibility to severe COVID-19 share a common genetic mechanism involved in the immune response to viruses, researchers report. The results could lead to new treatment goals to slow the progression and severity of both diseases.
Investigators found that a single genetic variant in the oligoadenylate synthetase 1 (OAS1) gene increased the risk of AD and that related variants in the same gene increased the likelihood of severe COVID-19 results.
“These results could allow us to identify new drug targets to slow the progression of both diseases and reduce their severity,” Dervis Salih, PhD, senior research fellow at the UK Dementia Research Institute, University College London, UK, told Medscape Medical News.
“Our work also suggests new approaches to treating both diseases with the same drugs,” added Salih.
The study was published online in Brain on October 7th.
Common genetic network
The OAS1 gene is expressed in microglia, a type of immune cell that makes up about 10% of all cells in the brain.
In previous work, the researchers found evidence of a link between the OAS1 gene and AD, but the function of the gene in microglia was unknown.
To further investigate the gene’s link to AD, they sequenced genetic data from 2,547 people – half with AD and the other half.
Genotyping analysis confirmed that the single nucleotide polymorphism (SNP) rs1131454 within OAS1 is significantly associated with AD.
Since the same OAS1 locus has recently been linked to severe COVID-19 results, the researchers examined four variants of the OAS1 gene.
The results show that SNPs within OAS1 associated with AD are also linked to SNP variants associated with critical illness in COVID-19.
rs1131454 (risk allel A) and rs4766676 (risk allel T) have been linked to AD, and rs10735079 (risk allel A) and rs6489867 (risk allel T) have been linked to serious illness with COVID-19, investigators report. All of these risk alleles attenuate the expression of OAS1.
“This study also provides strong new evidence that interferon signaling by the innate immune system is essential in the progression of Alzheimer’s disease,” said Salih.
“Identifying this common genetic network in cells of the innate immune system will enable us in the future to identify new biomarkers to track disease progression and better predict disease risk for both diseases,” he added.
“Fascinating” link
In a statement from the UK nonprofit Science Media Center, Kenneth Baillie, MBChB, of the University of Edinburgh said this study builds on a discovery he and his colleagues made last year that OAS1 variants are associated with severe COVID-19 stay in contact.
“In the ISARIC4C study we recently found that this was likely due to a change in the way cell membranes recognize viruses, but that mechanism does not explain the fascinating Alzheimer’s disease link that is discussed in this new paper is reported, ”said Baillie.
“It is often the case that the same gene can have different roles in different parts of the body. The important thing is that COVID-19 disease does not affect your Alzheimer’s risk, ”he added.
Jonathan Schott, MD, Professor of Neurology at University College London, also paid tribute to the new study, noting that dementia is the “main pre-existing health condition associated with COVID-19 mortality, accounting for approximately 1 in 4 deaths from COVID-19 between “March and June 2020.
“Although some of this excessive mortality could be due to the fact that people with dementia are overrepresented in nursing homes that have been particularly hard hit by the pandemic, or because they are generally more susceptible to infection, it was asked whether there are common factors that potentially increase susceptibility to both developing dementia and dying from COVID-19, “said Schott.
This “elegant paper” provides evidence of the latter, “suggesting a common genetic mechanism for both Alzheimer’s disease and severe COVID-19 infection,” said Schott.
“Identifying a genetic risk factor and unraveling the inflammatory pathways that may increase the risk has important implications for our understanding of both diseases, with potential implications for new treatments,” he added.
The study was funded by the UK Dementia Research Institute. The authors have not disclosed any relevant financial relationships. Schott is Chief Medical Officer of Alzheimer’s Research UK and clinical advisor to the UK Dementia Research Institute. Baillie has not disclosed any relevant financial relationships.
Brain. Published online October 7, 2021. Full text
Visit us on Facebook and Twitter to learn more about Medscape Psychiatry.
