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s40478-022-01415-7.pdf (1.65 MB)

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2022-08-17

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cc by (c) Gelpi, Ellen et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/188966

Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

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https://doi.org/10.1186/s40478-022-01415-7

Resum

The methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype.

Matèries

Malalties per prions, Malaltia de Creutzfeldt-Jakob

Matèries (anglès)

Prion diseases, Creutzfeldt-Jakob disease

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

GELPI, Ellen, BAIARDI, Simone, NOS, Carlos, DELLAVALLE, Sofia, ALDECOA, Iban, RUIZ GARCIA, Raquel, ISPIERTO, Lourdes, ESCUDERO, Domingo, CASADO, Virgina, BARRANCO, Elena, BOLTES, Anuncia, MOLINA PORCEL, Laura, BARGALLÓ ALABART, Núria​, ROSSI, Marcello, MAMMANA, Angela, TIPLE, Dorina, VAIANELLA, Luana, STOEGMANN, Elisabeth, SIMONITSCH KLUPP, Ingrid, KASPRIAN, Gregor, KLOTZ, Sigrid, HÖFTBERGER, Romana, BUDKA, Herbert, KOVACS, Gabor g., FERRER, Isidro (ferrer abizanda), CAPELLARI, Sabina, SÁNCHEZ VALLE, Raquel, PARCHI, Piero. Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease. _Acta Neuropathologica Communications_. 2022. Vol. 10, núm. 1. [consulta: 24 de gener de 2026]. ISSN: 2051-5960. [Disponible a: https://hdl.handle.net/2445/188966]

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