A genetic link shared between Alzheimer’s disease and severe COVID-19


Alzheimer’s disease (AD) and severe COVID-19 share genetic risk factor, study results published in journal Brain indicate that a genetic variant previously associated with severe COVID-19 findings is also associated with an increased risk of AD.

Previous studies have shown an association between oligoadenylate synthetase 1 (OAS1), an antiviral gene expressed in microglia, with an increased risk of AD.

Using the genotyping of 1313 patients (mean age at death, 76.7 years; 60.9% women) with sporadic AD and 1234 control individuals (mean age at death, 72.6 years; 53% women ), the researchers evaluated 4 variants of the OAS1 gene that slows down its expression: rs1131454 and rs4766676 (associated with AD) and rs10735079 and rs6489867 (associated with severe illness with COVID-19).


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Analysis indicated that genetic variants within OAS1 associated with AD show a linkage imbalance with severe disease-associated variants in COVID-19.

Study of the transcriptome expressed by microglia and macrophages has indicated gene co-expression networks made up of genes in interferon response pathways. The data suggests that OAS1 is expressed alongside interferon-sensitive genes in microglia and alveolar macrophages, and may play a role in the interferon response in both myeloid subtypes. This response is upregulated during severe cases of COVID-19, aging, and amyloid disease.

reversal of OAS1 expression using small interfering RNAs resulted in exaggerated production of pro-inflammatory cytokines with interferon gamma stimuli, suggesting that upregulation of interferon-sensitive genes with age may attenuate age-related damage by limiting pro-inflammatory signaling. Dysfunction of interferon signaling with a blunt response against pathogens secondary to genetic variants is associated with an increased risk of developing AD and severe COVID-19.

“[O]Our data support a link between the genetic risk of Alzheimer’s disease and susceptibility to serious illness with COVID-19 focused on OAS1, a discovery with potential implications for future treatments for Alzheimer’s disease and COVID-19, and the development of biomarkers to track disease progression, ”the researchers concluded.

Disclosure: One study author reported affiliations with biotech, pharmaceutical, and / or device companies. Please see the original reference for a full list of author disclosures.

Reference

Magusali N, Graham AC, Piers TM, et al. A genetic link between the risk of Alzheimer’s disease and the serious consequences of COVID-19 via the OAS1 uncomfortable. Brain. Published online October 7, 2021. doi: 10.1093 / brain / awab337


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