{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:00Z","timestamp":1787008560532,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Catherine and Michael Heagerty"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Astrocytes are glial cells of the central nervous system that become reactive under conditions of stress. The functional properties of reactive astrocytes depend on their stimulus that induces the upregulation of specific genes. Reactive astrocytes are a neuropathological feature of prion disorders; however, their role in the disease pathogenesis is not well understood. Here, we describe our studies of one polarization state of reactive astrocytes, termed A1 astrocytes, in the frontal cortex region of 35 human sporadic Creutzfeldt\u2013Jakob disease brains encompassing a range of molecular sub-types. Examination of two mRNA markers of A1 astrocytes, C3 and GBP2, revealed a strong linear correlation between the two following their log-normalization (P\u2009=\u20090.0011). Both markers were found upregulated in the sporadic Creutzfeldt\u2013Jakob disease brain compared with age-matched control tissues (P\u2009=\u20090.0029 and 0.0002, for C3log and GBP2log, respectively), and stratifying samples based on codon 129 genotype revealed that C3log is highest in homozygous methionine and lowest in homozygous valine patients, which followed a linear trend (P\u2009=\u20090.027). Upon assessing other disease parameters, a significant positive correlation was found between GBP2log and disease duration (P\u2009=\u20090.031). These findings provide evidence for a divergence in the astrocytic environment amongst patients with sporadic Creutzfeldt\u2013Jakob disease based on molecular sub-type parameters of disease. While more research will be needed to determine the global changes in the genomic profiles and resulting functional properties of reactive astrocytes in disease, considering the evidence demonstrating that A1 astrocytes harbour neurotoxic properties, the changes seen in C3log and GBP2log in the current study may reflect differences in pathogenic mechanisms amongst the sporadic Creutzfeldt\u2013Jakob disease sub-types associated with the A1 polarization state.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa029","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T10:17:37Z","timestamp":1584440257000},"source":"Crossref","is-referenced-by-count":37,"title":["Markers of A1 astrocytes stratify to molecular sub-types in sporadic Creutzfeldt\u2013Jakob disease brain"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-6437","authenticated-orcid":false,"given":"Cathryn L","family":"Ugalde","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Lewis","sequence":"additional","affiliation":[{"name":"Australian National CJD Registry, Florey Institute of Neuroscience & Mental Health, Parkville, Victoria 3010, Australia"},{"name":"Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Stehmann","sequence":"additional","affiliation":[{"name":"Australian National CJD Registry, Florey Institute of Neuroscience & Mental Health, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona A","family":"McLean","sequence":"additional","affiliation":[{"name":"Australian National CJD Registry, Florey Institute of Neuroscience & Mental Health, Parkville, Victoria 3010, Australia"},{"name":"Department of Anatomical Pathology, Alfred Health, Melbourne, Victoria 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A","family":"Lawson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J","family":"Collins","sequence":"additional","affiliation":[{"name":"Australian National CJD Registry, Florey Institute of Neuroscience & Mental Health, Parkville, Victoria 3010, Australia"},{"name":"Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-2354","authenticated-orcid":false,"given":"Andrew F","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,17]]},"reference":[{"key":"2020080712361799100_fcaa029-B1","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1172\/JCI90605","article-title":"Microglia in prion diseases","volume":"127","author":"Aguzzi","year":"2017","journal-title":"J Clin Invest"},{"key":"2020080712361799100_fcaa029-B2","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0140-6736(99)01342-2","article-title":"Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob 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