{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:46:58Z","timestamp":1782190018663,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009192","name":"Alberta Innovates","doi-asserted-by":"publisher","award":["201700014"],"award-info":[{"award-number":["201700014"]}],"id":[{"id":"10.13039\/501100009192","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The MV1 subtype of sporadic Creutzfeldt\u2013Jakob disease (sCJD) is one of the least studied. Cases are defined by the presence of the methionine\/valine (MV) polymorphism at codon 129 of the\n                    <jats:italic>PRNP<\/jats:italic>\n                    gene and a type 1 immunoblot pattern of pathological prion protein (PrP\n                    <jats:sup>D<\/jats:sup>\n                    ), where the unglycosylated PrP\n                    <jats:sup>D<\/jats:sup>\n                    fragment migrates at ~21\u2009kDa (T\n                    <jats:sup>21<\/jats:sup>\n                    ). Because the originally described MV1 cases had T\n                    <jats:sup>21<\/jats:sup>\n                    plus brain pathology indistinguishable from MM1 cases (small vacuoles), the MV1 subtype has historically been grouped with MM1. However, the recent identification of MV1 cases with immunoblot and pathological features similar to the VV1 subtype (T\n                    <jats:sup>21\u201320<\/jats:sup>\n                    doublet, larger vacuoles, ballooned neurons) has raised the possibility that the MV1 subtype is more heterogeneous than originally proposed. Here, we report three MV1 cases that further reveal the heterogeneity of this subtype. All cases were atypical in that they had persistent T\n                    <jats:sup>20<\/jats:sup>\n                    fragments, in isolation or combination with T\n                    <jats:sup>21<\/jats:sup>\n                    or T\n                    <jats:sup>19<\/jats:sup>\n                    , when typed at pH\u20096.9, a finding that would have been missed if typing were undertaken at pH\u20098.0 only. Fragment proportions differed in different brain regions, and further examination found that the cases had mixed MM1\/VV1 features, predominant VV1\u2010like characteristics or features of the MV2C subtype. Two cases had small to intermediate\u2010sized vacuoles and synaptic PrP staining. The third case had intermediate vacuolation, weak synaptic staining and coarse PrP deposits. We also describe, for the first time, the application of asymmetric\u2010flow field\u2010flow fractionation as a novel tool to discriminate sCJD subtypes based on size distributions of protease\u2010resistant and protease\u2010sensitive PrP\n                    <jats:sup>D<\/jats:sup>\n                    . Overall, we propose that MV1 is a more heterogeneous subtype than previously appreciated, potentially existing along a spectrum from MM1\u2010like to VV1\u2010like phenotypes. Importantly, this biochemical heterogeneity may be underrepresented when subtyping is done at pH\u20098.0, so we recommend CJD subtyping be performed at pH\u20096.9 to avoid missing atypical or mixed cases.\n                  <\/jats:p>","DOI":"10.1111\/nan.70078","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:09:46Z","timestamp":1777975786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Understanding the Phenotypic Heterogeneity Within the Sporadic Creutzfeldt\u2013Jakob Disease MV1 Subtype"],"prefix":"10.1111","volume":"52","author":[{"given":"Satish K.","family":"Nemani","sequence":"first","affiliation":[{"name":"Centre for Prions and Protein Folding Diseases University of Alberta  Edmonton Alberta Canada"},{"name":"Division of Neurology, Department of Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo M.","family":"Cortez","sequence":"additional","affiliation":[{"name":"Centre for Prions and Protein Folding Diseases University of Alberta  Edmonton Alberta Canada"},{"name":"Division of Neurology, Department of Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Myskiw","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector\u2010Borne and Prion Diseases Division, National Microbiology Laboratory Public Health Agency of Canada  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio","family":"Cali","sequence":"additional","affiliation":[{"name":"Department of Pathology Case Western Reserve University  Cleveland Ohio USA"},{"name":"National Prion Disease Pathology Surveillance Center  Cleveland Ohio USA"},{"name":"Faculty of Medicine and Surgery \u2018Kore\u2019 University of Enna  Enna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Booth","sequence":"additional","affiliation":[{"name":"Mycobacteriology, Vector\u2010Borne and Prion Diseases Division, National Microbiology Laboratory Public Health Agency of Canada  Winnipeg Manitoba Canada"},{"name":"Department of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard H.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0088-8666","authenticated-orcid":false,"given":"Valerie L.","family":"Sim","sequence":"additional","affiliation":[{"name":"Centre for Prions and Protein Folding Diseases University of Alberta  Edmonton Alberta Canada"},{"name":"Division of Neurology, Department of Medicine University of Alberta  Edmonton Alberta Canada"},{"name":"Neurosciences and Mental Health Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/66.1.213"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390613"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531\u20108249(199908)46:2<224::AID\u2010ANA12>3.0.CO;2\u2010W"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.18.10168"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010010\u20100761\u20103"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010020\u201000966\u2010x"},{"key":"e_1_2_12_8_1","first-page":"271","volume-title":"Handbook of Clinical Neurology","author":"Cracco 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