{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:29:42Z","timestamp":1793118582499,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer\u2019s Society","award":["ARUK-MID2022"],"award-info":[{"award-number":["ARUK-MID2022"]}]},{"name":"ARUK project grant","award":["ARUK-MID2022"],"award-info":[{"award-number":["ARUK-MID2022"]}]},{"name":"Nottingham Trent University","award":["ARUK-MID2022"],"award-info":[{"award-number":["ARUK-MID2022"]}]},{"name":"Alzheimer\u2019s Research UK","award":["ARUK-MID2022"],"award-info":[{"award-number":["ARUK-MID2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The immune system and neuroinflammation are now well established in the aetiology of neurodegeneration. Previous studies of transcriptomic and gene association studies have highlighted the potential of the 2\u2032\u20135\u2032 oligoadenylate synthetase 1 (OAS1) to play a role in Alzheimer\u2019s disease. OAS1 is a viral response gene, interferon-induced, dsRNA activated enzyme, which binds RNase L to degrade dsRNA, and has been associated with COVID-19 response. This study explores whether a viral defence gene could play a vital role in neurodegeneration pathology. The genotyping of five SNPs across the OAS1 locus was conducted in the Brains for Dementia Research (BDR) Cohort for association with AD. RNA-sequencing data were explored for differences in OAS1 gene expression between phenotypes and genotypes. Finally, levels of dsRNA were measured in control cell lines, prior to and after exposure to amyloid oligomers and in cells harbouring a dementia-relevant mutation. No association of any of the OAS1 SNPs investigated were associated with the AD phenotype in the BDR cohort. However, gene expression data supported the previous observation that the minor allele haplotype was associated with higher levels of the OAS1 gene expression and the presence of an alternative transcript. Further to this, the presence of endogenous dsRNA was found to increase with exposure to amyloid oligomers and in the cell line with a dementia-relevant mutation. The data presented here suggest further exploration of the OAS1 gene in relation to dementia is warranted. Investigations of whether carriers of the protective OAS1 haplotype lower dsRNA presence and in turn lower inflammation and cell death are required to support the role of the gene as a moderator of neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms26020524","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T09:54:27Z","timestamp":1736416467000},"page":"524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["OAS1: A Protective Mechanism for Alzheimer\u2019s Disease? An Exploration of Data and Possible Mechanisms"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8504-9801","authenticated-orcid":false,"given":"Richard J.","family":"Elsworthy","sequence":"first","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8476-8685","authenticated-orcid":false,"given":"Alex","family":"Pearce","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnoush","family":"Masoudzadeh","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Koska","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honey","family":"Lodhiya","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gargi","family":"Meher","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodelle","family":"Adjej","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2427-2513","authenticated-orcid":false,"given":"Keeley J.","family":"Brookes","sequence":"additional","affiliation":[{"name":"Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham NG11 8NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/S1474-4422(21)00066-1","article-title":"Clinical diagnosis of Alzheimer\u2019s disease: Recommendations of the International Working Group","volume":"20","author":"Dubois","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. 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