Review: Creutzfeldt‐Jakob Disease

Ironside, James W.

doi:10.1111/j.1750-3639.1996.tb00869.x

Cited by 73 publications

(61 citation statements)

References 36 publications

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“…Therefore, comparing BSE with vCJD may provide guidance on how to approach the issue of possible transmission of CWD to humans. The histopathology and the PrP Sc immunohistochemistry of BSE are different from those of vCJD in the type and topography of the lesions as well as the pattern of the PrP Sc immunostaining (32,33). In BSE the lesions are most prominent in subcortical structures of the brain, especially basal ganglia, thalamus, hypothalamus, and selected regions of brain stem and spinal cord, whereas the cerebral and cerebellar cortices are minimally affected (33).…”

Section: Affected the Immunostaining Shows A Prpmentioning

confidence: 99%

Chronic Wasting Disease of Elk and Deer and Creutzfeldt-Jakob Disease

Xie

O’Rourke

Dong

et al. 2006

Journal of Biological Chemistry

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Chronic wasting disease (CWD), a transmissible prion disease that affects elk and deer, poses new challenges to animal and human health. Although the transmission of CWD to humans has not been proven, it remains a possibility. If this were to occur, it is important to know whether the "acquired" human prion disease would show a phenotype including the scrapie prion protein (PrP Sc ) features that differ from those associated with human sporadic prion disease. In this study, we have compared the pathological profiles and PrP Sc characteristics in brains of CWD-affected elk and deer with those in subjects with sporadic Creutzfeldt-Jakob disease (CJD), as well as CJD-affected subjects who might have been exposed to CWD, using histopathology, immunohistochemistry, immunoblotting, conformation stability assay, and N-terminal protein sequencing. Spongiform changes and intense PrP Sc staining were present in several brain regions of CWD-affected animals. Immunoblotting revealed three proteinase K (PK)-resistant bands in CWD, representing different glycoforms of PrP Sc . The unglycosylated PK-resistant PrP Sc of CWD migrated at 21 kDa with an electrophoretic mobility similar to that of type 1 human PrP Sc present in sporadic CJD affecting subjects homozygous for methionine at codon 129 (sCJDMM1). N-terminal sequencing showed that the PK cleavage site of PrP Sc in CWD occurred at residues 82 and 78, similar to that of PrP Sc in sCJDMM1. Conformation stability assay also showed no significant difference between elk CWD PrP Sc and the PrP Sc species associated with sCJDMM1. However, there was a major difference in glycoform ratio of PrP Sc between CWD and sCJDMM1 affecting both subjects potentially exposed to CWD and non-exposed subjects. Moreover, PrPSc of CWD exhibited a distinct constellation of glycoforms distinguishable from that of sCJDMM1 in two-dimensional immunoblots. These findings underline the importance of detailed PrP Sc characterization in trying to detect novel forms of acquired prion disease.

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Section: Affected the Immunostaining Shows A Prpmentioning

confidence: 99%

Chronic Wasting Disease of Elk and Deer and Creutzfeldt-Jakob Disease

Xie

O’Rourke

Dong

et al. 2006

Journal of Biological Chemistry

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“…5,13 Florid plaques, which consist of PrP res accumulations surrounded by vacuoles, are considered pathognomonic for variant Creutzfeldt-Jakob Disease in humans. 11,21 Staining of PrP res in the plexiform layers of retina has been described previously in scrapie-affected sheep. 10,12 However, in elk retina the PrP res also multifocally extended into the ganglion cell layer.…”

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confidence: 99%

Transmission of Sheep Scrapie to Elk (Cervus Elaphus Nelsoni) by Intracerebral Inoculation: Final Outcome of the Experiment

et al. 2004

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Abstract. This is a final report of an experimental transmission of sheep scrapie agent by intracerebral inoculation to Rocky Mountain elk (Cervus elaphus nelsoni). It documents results obtained in experimental (n ϭ 6) and control (n ϭ 2) elk. During the first 2 years postinoculation (PI), 3 animals died or were euthanized because of infection or injuries other than spongiform encephalopathy (SE). In years 3 and 4 PI, 3 other inoculated elk died after brief terminal neurological episodes. Necropsy of these animals revealed moderate weight loss but no other gross lesions. Microscopically, characteristic lesions of SE were seen throughout the brain and spinal cord, and the tissue was positive for proteinase K-resistant prion protein (PrP res ) by immunohistochemistry (IHC) and by Western blot. Scrapie-associated fibrils (SAF) were observed by negative-stain electron microscopy in the brain of elk with neurologic signs. PrP res and SAF were not detected in the 3 inoculated elk necropsied during the first 2 years or in the 2 control animals. Retrospective analysis of the gene-encoding cervid PrP revealed a polymorphism at codon 132. The elk with SE were either homozygous (MM) or heterozygous (LM). These findings confirm that intracerebral inoculation of sheep scrapie agent results in SE with accumulations of PrP res in the central nervous system of elk. Based on morphologic and IHC findings, the experimentally induced SE cannot be distinguished from chronic wasting disease of elk with currently available diagnostic techniques.Experimental cross-species transmission of transmissible spongiform encephalopathy (TSE) agents provides valuable information for identification of potential host ranges of known TSEs. 17 Scrapie is a naturally occurring TSE of sheep and goats and has been proposed as a possible source of chronic wasting disease (CWD) in cervids. 22 Transmissible spongiform encephalopathy-infected animals have accumulations of an abnormal form of prion protein (PrP res ) in tissues of the CNS and lymphatic system. Detection of PrP res in these tissues and characteristic histopathological changes in the brain are the basis of currently available diagnostic methods for TSEs. 9 In a previous publication, preliminary findings of experimental inoculation of sheep scrapie to elk through the intracerebral route were documented. 7 This communication describes details of clinicopathological results of the study that was terminated in the fall of 2002, approximately 4 years after the study was initiated.Experimental design, biocontainment protocol, selection of inoculum, inoculation procedure, sample collection, and diagnostic test methods have been published previously. 7 Briefly, the experiment involved 8, 3-to 4-month-old male castrated elk calves. The calves were assigned to scrapieinoculated (n ϭ 6) and control (n ϭ 2) groups. A detailed necropsy was conducted within 1 hour after death or euthanasia of the animals. Tissue samples for histopathology were immersion fixed in 10% neutral buffered formalin for not less ...

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“…Variant Creutzfeldt-Jakob disease (vCJD) is a member of the group of diseases known as the transmissible spongiform encephalopathies or prion diseases [1,2]. These are rare fatal neurodegenerative disorders that occur in humans and mammals, the best known examples in non-human species being scrapie in sheep and bovine spongiform encephalopathy (BSE) in cattle.…”

Section: Introductionmentioning

confidence: 99%

“…Alzheimer's disease, the disease progression is rapid and the majority of patients are dead within 6 months of disease onset [8]. The accumulation of PrP Sc in sporadic CJD appears to be confined to the central nervous system and sensory ganglia [1,11]. There have been a number of case-control studies to investigate whether blood transfusion is a risk factor for sporadic CJD, and the evidence appears reassuring that this is not the case [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Variant Creutzfeldt–Jakob disease and its transmission by blood

Ironside

Head

2003

Journal of Thrombosis and Haemostasis

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Summary. Variant Creutzfeldt–Jakob disease (vCJD) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (BSE). vCJD differs from all other human prion diseases in that the disease‐associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell‐associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease‐associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease‐associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD.

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Review: Creutzfeldt‐Jakob Disease

Cited by 73 publications

References 36 publications

Chronic Wasting Disease of Elk and Deer and Creutzfeldt-Jakob Disease

Chronic Wasting Disease of Elk and Deer and Creutzfeldt-Jakob Disease

Transmission of Sheep Scrapie to Elk (Cervus Elaphus Nelsoni) by Intracerebral Inoculation: Final Outcome of the Experiment

Variant Creutzfeldt–Jakob disease and its transmission by blood

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