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Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata-Possible Routes of Infection and Host Susceptibility.

Iacono D, Ferrari S, Gelati M, Zanusso G, Mariotto S, Monaco S - Biomed Res Int (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

(a) Anti-PrPSc staining of the inferior olivary complex (IOC): inferior olivary nucleus (A) and accessory olivary nucleus (B) in patient number 14; (b) shows perihypoglossal nuclei: nucleus praepositus (A), nucleus intercalatus (B), and the nucleus of Roller (C), stained with anti-PrP antibody in the same case (bar = 200 μm).
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fig1: (a) Anti-PrPSc staining of the inferior olivary complex (IOC): inferior olivary nucleus (A) and accessory olivary nucleus (B) in patient number 14; (b) shows perihypoglossal nuclei: nucleus praepositus (A), nucleus intercalatus (B), and the nucleus of Roller (C), stained with anti-PrP antibody in the same case (bar = 200 μm).

Mentions: The perihypoglossal nuclei (PHN, including nucleus praepositus, nucleus intercalatus, and the nucleus of Roller) and the inferior olivary complex (IOC, including the medial and dorsal accessory olive and the inferior olive) were considered as whole groups (Figure 1).


Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata-Possible Routes of Infection and Host Susceptibility.

Iacono D, Ferrari S, Gelati M, Zanusso G, Mariotto S, Monaco S - Biomed Res Int (2015)

(a) Anti-PrPSc staining of the inferior olivary complex (IOC): inferior olivary nucleus (A) and accessory olivary nucleus (B) in patient number 14; (b) shows perihypoglossal nuclei: nucleus praepositus (A), nucleus intercalatus (B), and the nucleus of Roller (C), stained with anti-PrP antibody in the same case (bar = 200 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4589575&req=5

fig1: (a) Anti-PrPSc staining of the inferior olivary complex (IOC): inferior olivary nucleus (A) and accessory olivary nucleus (B) in patient number 14; (b) shows perihypoglossal nuclei: nucleus praepositus (A), nucleus intercalatus (B), and the nucleus of Roller (C), stained with anti-PrP antibody in the same case (bar = 200 μm).
Mentions: The perihypoglossal nuclei (PHN, including nucleus praepositus, nucleus intercalatus, and the nucleus of Roller) and the inferior olivary complex (IOC, including the medial and dorsal accessory olive and the inferior olive) were considered as whole groups (Figure 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus