{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:21:09Z","timestamp":1791249669319,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute","award":["RF-2013-02359816"],"award-info":[{"award-number":["RF-2013-02359816"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Gerstmann\u2013Str\u00e4ussler\u2013Scheinker disease (GSS) is a rare genetic prion disease. A large GSS kindred linked to the serine-for-phenylalanine substitution at codon 198 of the prion protein gene (GSS-F198S) is characterized by conspicuous accumulation of prion protein (PrP)-amyloid deposits and neurofibrillary tangles. Recently, we demonstrated the transmissibility of GSS-F198S prions to bank vole carrying isoleucine at 109 PrP codon (BvI). Here we investigated: (i) the transmissibility of GSS-F198S prions to voles carrying methionine at codon 109 (BvM); (ii) the induction of hyperphosphorylated Tau (pTau) in two vole lines, and (iii) compared the phenotype of GSS-F198S-induced pTau with pTau induced in BvM following intracerebral inoculation of a familial Alzheimer\u2019s disease case carrying Presenilin 1 mutation (fAD-PS1). We did not detect prion transmission to BvM, despite the high susceptibility of BvI previously observed. Immunohistochemistry established the presence of induced pTau depositions in vole brains that were not affected by prions. Furthermore, the phenotype of pTau deposits in vole brains was similar in GSS-F198S and fAD-PS1. Overall, results suggest that, regardless of the cause of pTau deposition and its relationship with PrPSc in GSS-F198S human-affected brains, the two components possess their own seeding properties, and that pTau deposition is similarly induced by GSS-F198S and fAD-PS1.<\/jats:p>","DOI":"10.3390\/biom12101537","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"1537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Gerstmann\u2013Str\u00e4ussler\u2013Scheinker Disease with F198S Mutation Induces Independent Tau and Prion Protein Pathologies in Bank Voles"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-8109","authenticated-orcid":false,"given":"Rosalia","family":"Bruno","sequence":"first","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pirisinu","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldina","family":"Riccardi","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"De Cecco","sequence":"additional","affiliation":[{"name":"Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), 34136 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-4393","authenticated-orcid":false,"given":"Giuseppe","family":"Legname","sequence":"additional","affiliation":[{"name":"Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), 34136 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2376-0470","authenticated-orcid":false,"given":"Franco","family":"Cardone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gambetti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7556-1564","authenticated-orcid":false,"given":"Romolo","family":"Nonno","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Agrimi","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-6823","authenticated-orcid":false,"given":"Michele Angelo","family":"Di Bari","sequence":"additional","affiliation":[{"name":"Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanita\u2019, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Farlow, M.R. (2014). Gerstmann\u2013Str\u00e4ussler\u2013Scheinker Syndrome. Encyclopedia of the Neurological Sciences, Elsevier.","DOI":"10.1016\/B978-0-12-385157-4.00378-X"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/ng0492-64","article-title":"Linkage of the Indiana kindred of Gerstmann-Str\u00e4ussler-Scheinker disease to the prion protein gene","volume":"1","author":"Dlouhy","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1212\/WNL.39.11.1453","article-title":"Gerstmann-str\u00e4ussler-scheinker disease. II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family","volume":"39","author":"Ghetti","year":"1989","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF02778006","article-title":"Familial Gerstmann-Str\u00e4ussler-Scheinker disease with neurofibrillary tangles","volume":"8","author":"Ghetti","year":"1994","journal-title":"Mol. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/1097-0029(20000701)50:1<10::AID-JEMT3>3.0.CO;2-6","article-title":"Neuropathology of Gerstmann-Straussler-Scheinker Disease","volume":"15","author":"Bugiani","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s00401-002-0547-3","article-title":"Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Str\u00e4ussler-Scheinker syndrome P102L mutation complicated with dementia","volume":"104","author":"Ishizawa","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11010-007-9664-6","article-title":"Human tau protein forms complex with PrP and some GSS- and fCJD-related PrP mutants possess stronger binding activities with tau in vitro","volume":"310","author":"Wang","year":"2008","journal-title":"Mol. Cell. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s40478-018-0608-z","article-title":"Detection of tau in Gerstmann-Str\u00e4ussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET","volume":"6","author":"Risacher","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0006-8993(93)90226-D","article-title":"A68 is a component of paired helical filaments of Gerstmann-Str\u00e4ussler-Scheinker disease, Indiana kindred","volume":"616","author":"Tagliavini","year":"1993","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00401-021-02336-w","article-title":"Structure of Tau filaments in Prion protein amyloidoses","volume":"142","author":"Hallinan","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12481","article-title":"Self-propagation of pathogenic protein aggregates in neurodegenerative diseases","volume":"501","author":"Jucker","year":"2013","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1146\/annurev-neuro-071714-033828","article-title":"Neurodegenerative Diseases: Expanding the Prion Concept","volume":"38","author":"Walker","year":"2015","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ncb1901","article-title":"Transmission and spreading of tauopathy in transgenic mouse brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.1073\/pnas.1301175110","article-title":"Brain homogenates from human tauopathies induce tau inclusions in mouse brain","volume":"110","author":"Clavaguera","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1099\/vir.0.2008\/005520-0","article-title":"The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie","volume":"89","author":"Chianini","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Di Bari, M.A., Nonno, R., Castilla, J., D\u2019Agostino, C., Pirisinu, L., Riccardi, G., Conte, M., Richt, J., Kunkle, R., and Langeveld, J. (2013). Chronic Wasting Disease in Bank Voles: Characterisation of the Shortest Incubation Time Model for Prion Diseases. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003219"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e02390-16","DOI":"10.1128\/JVI.02390-16","article-title":"Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease","volume":"91","author":"Galeno","year":"2017","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nonno, R., Di Bari, M.A., Cardone, F., Vaccari, G., Fazzi, P., Dell\u2019Omo, G., Cartoni, C., Ingrosso, L., Boyle, A., and Galeno, R. (2006). Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020012"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3201\/eid2501.180807","article-title":"Variable Protease-Sensitive Prionopathy Transmission to Bank Voles","volume":"25","author":"Nonno","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20443","DOI":"10.1038\/srep20443","article-title":"Gerstmann-Str\u00e4ussler-Scheinker disease subtypes efficiently transmit in bank voles as genuine prion diseases","volume":"6","author":"Pirisinu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.jchromb.2006.08.016","article-title":"Quantitative profiling of the pathological prion protein allotypes in bank voles by liquid chromatography-mass spectrometry","volume":"849","author":"Cartoni","year":"2007","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31417","DOI":"10.1073\/pnas.2013237117","article-title":"Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America","volume":"117","author":"Nonno","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41598-019-57005-6","article-title":"Characterization of goat prions demonstrates geographical variation of scrapie strains in Europe and reveals the composite nature of prion strains","volume":"10","author":"Nonno","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10660","DOI":"10.1128\/JVI.01592-16","article-title":"PrP C Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features","volume":"90","author":"Espinosa","year":"2016","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pirisinu, L., Di Bari, M.A., D\u2019Agostino, C., Vanni, I., Riccardi, G., Marcon, S., Vaccari, G., Chiappini, B., Benestad, S.L., and Agrimi, U. (2022). A single amino acid residue in bank vole prion protein drives permissiveness to Nor98\/atypical scrapie and the emergence of multiple strain variants. PLOS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010646"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/978-1-61779-551-0_31","article-title":"The Mouse Model for Scrapie: Inoculation, Clinical Scoring, and Histopathologi-cal Techniques","volume":"849","author":"Nonno","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.vetmic.2006.02.017","article-title":"BSE infection in bovine PrP transgenic mice leads to hyperphosphorylation of tau-protein","volume":"115","author":"Bautista","year":"2006","journal-title":"Vet. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jns.2017.10.040","article-title":"Variable tau accumulation in murine models with abnormal prion protein deposits","volume":"383","author":"Piccardo","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/jnen\/nlaa109","article-title":"Risk of transmissibility from neurodegenerative disease-associated proteins: Experimental knowns and unknowns","volume":"79","author":"Asher","year":"2021","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40478-017-0503-z","article-title":"Iatrogenic Creutzfeldt-Jakob disease with Amyloid-\u03b2 pathology: An international study","volume":"6","author":"Cali","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41586-018-0790-y","article-title":"Transmission of amyloid-\u03b2 protein pathology from cadaveric pituitary growth hormone","volume":"564","author":"Purro","year":"2018","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00401-017-1703-0","article-title":"Amyloid-\u03b2 accumulation in the CNS in human growth hormone recipients in the UK","volume":"134","author":"Ritchie","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1073\/pnas.93.2.744","article-title":"Vascular variant of prion protein cerebral amyloidosis with \u03c4-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP","volume":"93","author":"Ghetti","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:59:03Z","timestamp":1760144343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,21]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101537"],"URL":"https:\/\/doi.org\/10.3390\/biom12101537","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,21]]}}}