{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:56:23Z","timestamp":1767830183905,"version":"3.49.0"},"reference-count":23,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Fatal familial insomnia (FFI) belongs to the genetic human transmissible spongiform encephalopathies (TSE), such as genetic Creutzfeldt-Jakob disease (CJD) or Gerstmann-Straeussler-Scheinker syndrome (GSS). Here, we analyzed the properties of the pathological prion protein in six FFI cases by Western blot analysis, a protein aggregate stability assay, and aggregate deposition characteristics visualized with the paraffin-embedded tissue blot. While in all cases the unglycosylated fragment in Western blot analysis shared the same size with sporadic CJD prion type 2, the reticular\/synaptic deposition pattern of the prion aggregates resembled the ones found in sporadic CJD type 1 (CJD types according to the Parchi classification from 1999). Regarding the conformational stability against denaturation with GdnHCl, FFI prion aggregates resembled CJD type 1 more than type 2. Our results suggest that the size of the proteinase-K-resistant fragments is not a valid criterion on its own. Additional criteria supplying information about conformational differences or similarities need to be taken into account. FFI may resemble a prion type with its own conformation sharing properties partly with type 1 and type 2 prions.<\/jats:p>","DOI":"10.3390\/pathogens10101293","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:26:20Z","timestamp":1633728380000},"page":"1293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Defining the Prion Type of Fatal Familial Insomnia"],"prefix":"10.3390","volume":"10","author":[{"given":"Wiebke","family":"J\u00fcrgens-Wemheuer","sequence":"first","affiliation":[{"name":"Institute of Neuropathology, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Wrede","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-2322","authenticated-orcid":false,"given":"Walter","family":"Schulz-Schaeffer","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany"},{"name":"Prion and Dementia Research Unit, Department of Neuropathology, University Medical Center G\u00f6ttingen, Georg August University of G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.6801762","article-title":"Novel proteinaceous infectious particles cause scrapie","volume":"216","author":"Prusiner","year":"1982","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJM198610163151605","article-title":"Fatal Familial Insomnia and Dysautonomia with Selective Degeneration of Thalamic Nuclei","volume":"315","author":"Lugaresi","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1750-3639.1995.tb00576.x","article-title":"Fatal Familial Insomnia and Familial Creutzfeldt-Jakob Disease: Clinical, Pathological and Molecular Features","volume":"5","author":"Gambetti","year":"1995","journal-title":"Brain Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/ana.410380107","article-title":"Regional distribution of protease-resistant prion protein in fatal familial insomnia","volume":"38","author":"Parchi","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.1439789","article-title":"Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Disease phenotype determined by a DNA polymorphism","volume":"258","author":"Goldfarb","year":"1992","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/376434a0","article-title":"First experimental transmission of fatal familial insomnia","volume":"376","author":"Tateishi","year":"1995","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0002-9440(10)64705-0","article-title":"The paraffin-embedded tissue blot detects PrP(Sc) early in the incubation time in prion diseases","volume":"156","author":"Kranefuss","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/jnnp-2013-305978","article-title":"A proposal of new diagnostic pathway for fatal familial insomnia","volume":"85","author":"Krasnianski","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1073\/pnas.91.7.2839","article-title":"Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Different prion proteins determined by a DNA polymorphism","volume":"91","author":"Monari","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","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. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1056\/NEJM199202133260704","article-title":"Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene","volume":"326","author":"Medori","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.2353\/ajpath.2009.090623","article-title":"Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types","volume":"175","author":"Wemheuer","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3389\/fnagi.2017.00187","article-title":"Types and Strains: Their Essential Role in Understanding Protein Aggregation in Neurodegenerative Diseases","volume":"9","author":"Wemheuer","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/NEN.0b013e31829d2799","article-title":"Filtration of Protein Aggregates Increases the Accuracy for Diagnosing Prion Diseases in Brain Biopsies","volume":"72","author":"Wemheuer","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.vetmic.2011.12.008","article-title":"Detergents modify proteinase K resistance of PrP Sc in different transmissible spongiform encephalopathies (TSEs)","volume":"157","author":"Breyer","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_16","unstructured":"Zanusso, G. Evidence from Molecular Strain Typing. Proceedings of the Prion Conference PRION20210."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"fcz045","DOI":"10.1093\/braincomms\/fcz045","article-title":"Two distinct prions in fatal familial insomnia and its sporadic form","volume":"1","author":"Takeuchi","year":"2019","journal-title":"Brain Commun."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1212\/WNL.52.9.1757","article-title":"A subtype of sporadic prion disease mimicking fatal familial insomnia","volume":"52","author":"Parchi","year":"1999","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/ana.25300","article-title":"Sporadic Fatal Insomnia in Europe: Phenotypic Features and Diagnostic Challenges","volume":"84","author":"Redaelli","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1074\/jbc.M112.423715","article-title":"Burial of the polymorphic residue 129 in amyloid fibrils of prion stop mutants","volume":"288","author":"Skora","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1126\/science.274.5295.2079","article-title":"Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity","volume":"274","author":"Telling","year":"1996","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s004390050204","article-title":"Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: A systematic analysis of predisposing mutations and allelic variation in the PRNP gene","volume":"98","author":"Windl","year":"1996","journal-title":"Hum. Genet."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/10\/1293\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:16Z","timestamp":1760166616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/10\/1293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":23,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["pathogens10101293"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10101293","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]}}}