{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:57:52Z","timestamp":1780480672477,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medizinisch-Wissenschaftlichen Fonds des Burgermeisters der Stadt Wien","award":["18097"],"award-info":[{"award-number":["18097"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In sporadic Creutzfeldt-Jakob disease, molecular subtypes are neuropathologically well identified by the lesioning profile and the immunohistochemical PrPd deposition pattern in the grey matter (histotypes). While astrocytic PrP pathology has been reported in variant CJD and some less frequent histotypes (e.g., MV2K), oligodendroglial pathology has been rarely addressed. We assessed a series of sCJD cases with the aim to identify particular histotypes that could be more prone to harbor oligodendroglial PrPd. Particularly, the MM2C phenotype, in both its more \u201cpure\u201d and its mixed MM1+2C or MV2K+2C forms, showed more frequent oligodendroglial PrP pathology in the underlying white matter than the more common MM1\/MV1 and VV2 histotypes, and was more abundant in patients with a longer disease duration. We concluded that the MM2C strain was particularly prone to accumulate PrPd in white matter oligodendrocytes.<\/jats:p>","DOI":"10.3390\/v13091796","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T21:36:58Z","timestamp":1631223418000},"page":"1796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Histotype-Dependent Oligodendroglial PrP Pathology in Sporadic CJD: A Frequent Feature of the M2C \u201cStrain\u201d"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-4187","authenticated-orcid":false,"given":"Ellen","family":"Gelpi","sequence":"first","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Medical University of Vienna, Austrian Reference Center for Human Prion Diseases (OERPE), 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-2852","authenticated-orcid":false,"given":"Sigrid","family":"Klotz","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Medical University of Vienna, Austrian Reference Center for Human Prion Diseases (OERPE), 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Vidal-Robau","sequence":"additional","affiliation":[{"name":"Department of Neurology, Bellvitge University Hospital, L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0388-7965","authenticated-orcid":false,"given":"Gerda","family":"Ricken","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnther","family":"Regelsberger","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Medical University of Vienna, Austrian Reference Center for Human Prion Diseases (OERPE), 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Medical University of Vienna, Austrian Reference Center for Human Prion Diseases (OERPE), 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ognian","family":"Kalev","sequence":"additional","affiliation":[{"name":"Department of Neuropathology\/Pathology, Kepler Universit\u00e4ts Klinikum, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Leoni","sequence":"additional","affiliation":[{"name":"Department of Neuropathology\/Pathology, Medical University Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1933-1577","authenticated-orcid":false,"given":"Herbert","family":"Budka","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"Gabor G.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 0S8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology and Department of Medicine, University of Toronto, Toronto, ON M5T 0S8, Canada"},{"name":"Laboratory Medicine Program & Krembil Brain Institute, University Health Network, Toronto, ON M5T 1M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1126\/science.1675487","article-title":"Molecular biology of prion diseases","volume":"252","author":"Prusiner","year":"1991","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1101\/SQB.1996.061.01.052","article-title":"A new variant of Creutzfeldt-Jakob disease: Neuropathological and clinical features","volume":"Volume 61","author":"Ironside","year":"1996","journal-title":"Cold Spring Harbor Symposia on Quantitative Biology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0002-9440(10)62252-3","article-title":"Subcellular localization of disease-associated prion protein in the human brain","volume":"166","author":"Preusser","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/neup.12652","article-title":"A case of MV2K subtype of sporadic Creutzfeldt-Jakob disease with florid-like plaques: Similarities and differences to variant Creutzfeldt-Jakob disease","volume":"40","author":"Zupan","year":"2020","journal-title":"Neuropathology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/neup.12505","article-title":"Sporadic Creutzfeldt-Jakob disease with glial PrPRes nuclear and perinuclear immunoreactivity","volume":"38","author":"Geijo","year":"2018","journal-title":"Neuropathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/glia.20909","article-title":"Tubulin polymerization-promoting protein (TPPP\/p25) is critical for oligodendrocyte differentiation","volume":"58","author":"Lehotzky","year":"2010","journal-title":"Glia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W","article-title":"Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects","volume":"46","author":"Parchi","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1001\/archneur.63.6.876","article-title":"Clinical features and diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease","volume":"63","author":"Krasnianski","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1007\/s00415-019-09537-0","article-title":"Diagnostic value of surrogate CSF biomarkers for Creutzfeldt-Jakob disease in the era of RT-QuIC","volume":"266","author":"Baiardi","year":"2019","journal-title":"J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00401-009-0585-1","article-title":"Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: An updated classification","volume":"118","author":"Parchi","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/neup.12261","article-title":"Sporadic MM2-thalamic\u2009+\u2009cortical Creutzfeldt-Jakob disease: Utility of diffusion tensor imaging in the detection of cortical involvement In Vivo","volume":"36","author":"Gaig","year":"2016","journal-title":"Neuropathology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/neup.12350","article-title":"An autopsied case of MV2K+ C-type sporadic Creutzfeldt-Jakob disease presenting with widespread cerebral cortical involvement and Kuru plaques","volume":"37","author":"Iwasaki","year":"2017","journal-title":"Neuropathology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/nan.12461","article-title":"Regional pattern of microgliosis in sporadic Creutzfeldt-Jakob disease in relation to phenotypic variants and disease progression","volume":"44","author":"Franceschini","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_14","first-page":"443","article-title":"Oligodendroglia metabolically support axons and contribute to neurodegeneration","volume":"487","author":"Lee","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e42156","DOI":"10.7554\/eLife.42156","article-title":"Oligodendrocytes regulate presynaptic properties and neurotransmission through BDNF signaling in the mouse brainstem","volume":"8","author":"Jang","year":"2019","journal-title":"eLife"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41583-019-0196-3","article-title":"The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function","volume":"20","author":"Fawcett","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e15784","DOI":"10.7554\/eLife.15784","article-title":"A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons","volume":"5","author":"Micheva","year":"2016","journal-title":"eLife"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1002\/glia.23618","article-title":"Glutamate versus GABA in neuron\u2013oligodendroglia communication","volume":"67","author":"Habermacher","year":"2019","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1093\/cercor\/bhy029","article-title":"Differential Dependence of GABAergic and Glutamatergic Neurons on Glia for the Establishment of Synaptic Transmission","volume":"29","author":"Turko","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/ana.410340617","article-title":"Parvalbumin-immunoreactive cortical neurons in Creutzfeldt-Jakob disease","volume":"34","author":"Ferrer","year":"1993","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1750-3639.1998.tb00188.x","article-title":"Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies","volume":"8","author":"Guentchev","year":"1998","journal-title":"Brain Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/nbdi.1999.0245","article-title":"Early destruction of the extracellular matrix around parvalbumin-immunoreactive interneurons in Creutzfeldt-Jakob disease","volume":"6","author":"Belichenko","year":"1999","journal-title":"Neurobiol. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1097\/00005072-199710000-00005","article-title":"Distribution of parvalbumin-immunoreactive neurons in brain correlates with hippocampal and temporal cortical pathology in Creutzfeldt-Jakob disease","volume":"56","author":"Guentchev","year":"1997","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ana.21465","article-title":"Multiple system atrophy: A primary oligodendrogliopathy","volume":"64","author":"Wenning","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00401-012-1002-8","article-title":"Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: An inter-rater study among surveillance centres in Europe and USA","volume":"124","author":"Parchi","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1046\/j.1365-2990.2000.00279.x","article-title":"Clinicopathological phenotype of codon 129 valine homozygote sporadic Creutzfeldt-Jakob disease","volume":"26","author":"Kovacs","year":"2000","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1006\/exnr.1998.6894","article-title":"Modifications of oligodendroglial cells in spongiform encephalopathies","volume":"154","author":"Chaunu","year":"1998","journal-title":"Exp. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/19336896.2018.1500076","article-title":"Altered gene transcription linked to astrocytes and oligodendrocytes in frontal cortex in Creutzfeldt-Jakob disease","volume":"12","author":"Ferrer","year":"2018","journal-title":"Prion"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/19336896.2021.1935105","article-title":"Differential astrocyte and oligodendrocyte vulnerability in murine Creutzfeldt-Jakob disease","volume":"15","author":"Carmona","year":"2021","journal-title":"Prion"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s00401-005-0012-1","article-title":"BSE immunohistochemical patterns in the brainstem: A comparison between UK and Italian cases","volume":"111","author":"Casalone","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1177\/0300985810387072","article-title":"Experimental classical bovine spongiform encephalopathy: Definition and progression of neural PrP immunolabeling in relation to diagnosis and disease controls","volume":"48","author":"Simmons","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1365-2990.2007.00800.x","article-title":"Immunohistochemistry for PrPSc in natural scrapie reveals patterns which are associated with the PrP genotype","volume":"33","author":"Spiropoulos","year":"2007","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Konold, T., Bone, G.E., Clifford, D., Chaplin, M.J., Cawthraw, S., Stack, M.J., and Simmons, M.M. (2012). Experimental H-type and L-type bovine spongiform encephalopathy in cattle: Observation of two clinical syndromes and diagnostic challenges. BMC Vet. Res., 8.","DOI":"10.1186\/1746-6148-8-22"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/9\/1796\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:59:21Z","timestamp":1760165961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/9\/1796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["v13091796"],"URL":"https:\/\/doi.org\/10.3390\/v13091796","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,9]]}}}