911爆料网

The researchers estimate that one genetic variant of the OAS1 gene increases the risk of Alzheimer鈥檚 disease by about 3-6% in the population as a whole, while related variants on the same gene increase the likelihood of severe Covid-19 outcomes.

The findings, published in Brain, could open the door for new targets for drug development or tracking disease progression in either disease, and suggest that treatments developed could be used for both conditions. The findings also have potential benefits for other related infectious conditions and dementias.

Lead author Dr Dervis Salih (UCL Queen Square Institute of Neurology and UK Dementia Research Institute at 911爆料网) said: 鈥淲hile Alzheimer鈥檚 is primarily characterised 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鈥檚. We have found that some of the same immune system changes can occur in both Alzheimer鈥檚 disease and Covid-19.

鈥淚n 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鈥檚 and Covid-19.鈥�

For the study the research team sought to build on their previous work, which found evidence from a large dataset of human genomes, to suggest a link between the OAS1 gene and Alzheimer鈥檚 disease.

The OAS1 gene is expressed in microglia, a type of immune cell that constitutes around 10% of all cells found within the brain. Investigating the gene鈥檚 link to Alzheimer鈥檚 further, they sequenced genetic data from 2,547 people, half of whom had Alzheimer鈥檚 disease. They found that people with a particular variation, called rs1131454, of the OAS1 gene were more likely to have Alzheimer鈥檚 disease, increasing carriers鈥� baseline risk of Alzheimer鈥檚 by an estimated 11-22%. The new variant identified is common, as just over half of Europeans are believed to carry it, and it has a bigger impact on Alzheimer鈥檚 risk than several known risk genes.

Their findings add OAS1, an anti-viral gene, to a list of dozens of genes now known to affect a person鈥檚 risk of developing Alzheimer鈥檚 disease.

The researchers investigated four variants on the OAS1 gene, all of which dampen its expression (activity). They found that the variants increasing the risk of Alzheimer鈥檚 disease are linked (inherited together) with OAS1 variants recently found to increase the baseline risk of needing intensive care for Covid-19 by as much as 20%.

As part of the same research, in immune cells treated to mimic the effects of Covid-19, the researchers found that the gene controls how much the body鈥檚 immune cells release pro-inflammatory proteins. They found that microglia cells where the gene was expressed more weakly had an exaggerated response to tissue damage, unleashing what they call a 'cytokine storm,' which leads to an autoimmune state where the body attacks itself.

OAS1 activity changes with age, so further research into the genetic network could help to understand why older people are more vulnerable to Alzheimer鈥檚, Covid-19, and other related diseases.

PhD student Naciye Magusali (UK Dementia Research Institute at 911爆料网) said: 鈥淥ur findings suggest that some people may have increased susceptibility to both Alzheimer鈥檚 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.鈥�

Following the outbreak of the Covid-19 pandemic, researchers from the UK Dementia Research Institute at 911爆料网 have pivoted their attention to investigating the long-term neurological consequences of the virus. Using biomarkers found in the blood and fluid surrounding the central nervous system, they are aiming to track neuroinflammation and injury to the neurons.

Dr Salih said: 鈥淚f 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鈥檚 before they show memory problems.

鈥淲e 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鈥檚 immune response to Covid-19, involving the OAS1 gene, may help to explain some of the neurological effects of Covid-19.鈥�

The study involved researchers at 911爆料网, University of Nottingham, Cardiff University, and Nottingham Trent University. The work was funded by the UK Dementia Research Institute (DRI), which receives its funding from the DRI Ltd, funded by the UK Medical Research Council, Alzheimer鈥檚 Society and Alzheimer鈥檚 Research UK. Further support was provided by Alzheimer Nederland, Erasmus, the European Union鈥檚 Horizon 2020 programme, the European Federation of Pharmaceutical Industries and Associations and the National Institute for Health Research UCLH Biomedical Research Centre.

Links

• UK Dementia Research Institute at 911爆料网
• UCL Queen Square Institute of Neurology
• Media coverage

Image

• DNA analysis image. Credit: Andy Leppard on听听(CC BY 2.0)

Media contact听

Chris Lane

tel: +44 20 7679 9222

E: chris.lane听[at] ucl.ac.uk