title: Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata-Possible Routes of Infection and Host Susceptibility.
abstract: Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an "environmental exposure" might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a "triple match" hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors.
authors.affiliation: Neuropathology Research, Biomedical Research Institute of New Jersey, Cedar Knolls, NJ 07960, USA ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Iacono
authors.affiliation: Department of Neurological and Movement Sciences, Neurology and Neuropathology Unit, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department of Neurological and Movement Sciences, Neurology and Neuropathology Unit, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gelati
authors.affiliation: Department of Neurological and Movement Sciences, Neurology and Neuropathology Unit, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zanusso
authors.affiliation: Department of Neurological and Movement Sciences, Neurology and Neuropathology Unit, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mariotto
authors.affiliation: Department of Neurological and Movement Sciences, Neurology and Neuropathology Unit, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Monaco
mesh_terms: D000368:Aged; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions