Early pathologic and biochemical changes in Creutzfeldt-Jakob disease

Castellani, Rudy J.; Parchi, Piero; Stahl, J; Capellari, Sabina; Cohen, M.; Gambetti, Pierluigi

doi:10.1212/wnl.46.6.1690

Cited by 33 publications

(21 citation statements)

References 7 publications

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“…In natural and experimental TSEs, PrP Sc deposition represents an early event that occurs weeks to months before the development of spongiform changes (20,21). As a consequence, the detection of PrP Sc by Western immunoblot provides a unique opportunity in the diagnosis of BSE early in the incubation period and, therefore, in presymptomatic animals.…”

Section: Discussionmentioning

confidence: 99%

Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Casalone

Zanusso

Acutis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

412

406

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Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrP Sc ) of the host-encoded cellular prion protein (PrP C ). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrP Sc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called ''species barrier'' between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrP Sc accumulation. In addition, Western blot analysis showed a PrP Sc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrP Sc . Strikingly, the molecular signature of this previously undescribed bovine PrP Sc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.

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Section: Discussionmentioning

confidence: 99%

Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Casalone

Zanusso

Acutis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

412

406

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“…Diagnosis of prion diseases increasingly relies on immunoblot detection of PrP-res (23). In at least one GSS subtype, however, PrP-res has been reported to be undetectable, despite the demonstration of numerous PrP positive amyloid deposit (24).…”

Section: Discussionmentioning

confidence: 99%

Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann–Sträussler–Scheinker disease

Parchi

Chen

Brown

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

196

175

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The clinicopathological phenotype of the Gerstmann-Sträussler-Scheinker disease (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene (GSS P102L) shows a high heterogeneity. This variability also is observed in subjects with the same prion protein gene PRNP haplotype and is independent from the duration of the disease. Immunoblot analysis of brain homogenates from GSS P102L patients showed two major protease-resistant PrP fragments (PrP-res) with molecular masses of Ϸ21 and 8 kDa, respectively. The 21-kDa fragment, similar to the PrP-res type 1 described in Creutzfeldt-Jakob disease, was found in five of the seven subjects and correlated with the presence of spongiform degeneration and ''synaptic'' pattern of PrP deposition whereas the 8-kDa fragment, similar to those described in other variants of GSS, was found in all subjects in brain regions showing PrP-positive multicentric amyloid deposits. These data further indicate that the neuropathology of prion diseases largely depends on the type of PrP-res fragment that forms in vivo. Because the formation of PrP-res fragments of 7-8 kDa with ragged N and C termini is not a feature of Creutzfeldt-Jakob disease or fatal familial insomnia but appears to be shared by most GSS subtypes, it may represent a molecular marker for this disorder.

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“…Fresh and frozen tissue samples may increase diagnostic sensitivity. 24 As demonstrated by this case, a brain autopsy should be performed in patients who die of a progressive neurodegenerative disorder of unknown cause. Such testing is necessary to confirm the presence and type of most prion diseases.…”

Section: Figurementioning

confidence: 94%

Sporadic Fatal Insomnia in an Adolescent

et al. 2014

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The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient’s autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation.

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Early pathologic and biochemical changes in Creutzfeldt-Jakob disease

Cited by 33 publications

References 7 publications

Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann–Sträussler–Scheinker disease

Sporadic Fatal Insomnia in an Adolescent

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