{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:15:47Z","timestamp":1787008547357,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricerca Corrente"},{"DOI":"10.13039\/501100005969","name":"University of Bologna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricerca Fondamentale Orientata"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The current classification of sporadic Creutzfeldt\u2013Jakob disease identifies six major subtypes mainly defined by the combination of the genotype at polymorphic codon 129 (methionine\/M or valine\/V) of the prion protein gene and the type (1 or 2) of misfolded prion protein accumulating in the brain (e.g. MM1, MM2, MV1, MV2, etc.).<\/jats:p>\n                  <jats:p>Here, we systematically characterized the clinical and histo-molecular features associated with the third prevalent subtype, the MV2 subtype with kuru plaques (MV2K), in the most extensive series collected to date. We evaluated neurological histories, cerebrospinal biomarkers, brain MRI and EEG results in 126 patients. The histo-molecular assessment included misfolded prion protein typing, standard histologic staining and immunohistochemistry for prion protein in several brain areas. We also investigated the prevalence and topographic extent of coexisting MV2-cortical features, the number of cerebellar kuru plaques and their effect on clinical phenotype.<\/jats:p>\n                  <jats:p>Systematic regional typing revealed a western blot profile of misfolded prion protein comprising a doublet of 19 and 20 kDa unglycosylated fragments, with the former more prominent in neocortices and the latter in the deep grey nuclei. The 20\/19 kDa fragment ratio positively correlated with the number of cerebellar kuru plaques. The mean disease duration was exceedingly longer than in the typical MM1 subtype (18.0 versus 3.4 months). Disease duration correlated positively with the severity of pathologic change and the number of cerebellar kuru plaques. At the onset and early stages, patients manifested prominent, often mixed, cerebellar symptoms and memory loss, variably associated with behavioural\/psychiatric and sleep disturbances. The cerebrospinal fluid prion real-time quaking-induced conversion assay was positive in 97.3% of cases, while 14-3-3 protein and total-tau positive tests were 52.6 and 75.9%. Brain diffusion-weighted MRI showed hyperintensity of the striatum, cerebral cortex and thalamus in 81.4, 49.3 and 33.8% of cases, and a typical profile in 92.2%. Mixed histotypes (MV2K + MV2-cortical) showed an abnormal cortical signal more frequently than the pure MV2K (64.7 versus 16.7%, P = 0.007). EEG revealed periodic sharp-wave complexes in only 8.7% of participants.<\/jats:p>\n                  <jats:p>These results further establish MV2K as the most common \u2018atypical\u2019 subtype of sporadic Creutzfeldt\u2013Jakob disease, showing a clinical course that often challenges the early diagnosis. The plaque-type aggregation of the misfolded prion protein accounts for most of the atypical clinical features. Nonetheless, our data strongly suggest that the consistent use of the real-time quaking-induced conversion assay and brain diffusion-weighted MRI allows an accurate early clinical diagnosis in most patients.<\/jats:p>","DOI":"10.1093\/brain\/awad074","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T17:12:19Z","timestamp":1678122739000},"page":"3289-3300","source":"Crossref","is-referenced-by-count":16,"title":["Defining the phenotypic spectrum of sporadic Creutzfeldt\u2013Jakob disease MV2K: the kuru plaque type"],"prefix":"10.1093","volume":"146","author":[{"given":"Simone","family":"Baiardi","sequence":"first","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna , 40139 Bologna , Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , 40138 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Mammana","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna , 40139 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Dellavalle","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna , 40139 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Rossi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna , 40139 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Redaelli","sequence":"additional","affiliation":[{"name":"Neuropathology Unit, Fondazione I.R.C.S.S. Istituto Neurologico Carlo Besta , 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Colaizzo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Istituto Superiore di Sanit\u00e0 , 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Fede","sequence":"additional","affiliation":[{"name":"Neuropathology Unit, Fondazione I.R.C.S.S. Istituto Neurologico Carlo Besta , 20133 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ladogana","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Istituto Superiore di Sanit\u00e0 , 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1631-1439","authenticated-orcid":false,"given":"Sabina","family":"Capellari","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna , 40139 Bologna , Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , 40138 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-9524","authenticated-orcid":false,"given":"Piero","family":"Parchi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna , 40139 Bologna , Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , 40138 Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"2023080120210195300_awad074-B1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00401-015-1447-7","article-title":"The influence of PRNP polymorphisms on human prion disease susceptibility: An update","volume":"130","author":"Kobayashi","year":"2015","journal-title":"Acta Neuropathol"},{"key":"2023080120210195300_awad074-B2","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1002\/ana.410390613","article-title":"Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease","volume":"39","author":"Parchi","year":"1996","journal-title":"Ann 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Psychiatry"},{"key":"2023080120210195300_awad074-B6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/2051-5960-1-74","article-title":"Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M\/V and type 2 abnormal prion protein","volume":"1","author":"Kobayashi","year":"2013","journal-title":"Acta Neuropathol Commun"},{"key":"2023080120210195300_awad074-B7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s40478-020-00966-x","article-title":"A novel mechanism of phenotypic heterogeneity in Creutzfeldt-Jakob disease","volume":"8","author":"Nemani","year":"2020","journal-title":"Acta Neuropathol Commun"},{"key":"2023080120210195300_awad074-B8","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1093\/brain\/awl123","article-title":"Clinical findings and diagnostic tests in the MV2 subtype of sporadic 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