Pathological diagnosis of variant Creutzfeldt‐Jakob disease

Ironside, James W.; McCardle, Linda; Horsburgh, Avril; Lim, Zhi Wei; Head, Mark W.

doi:10.1034/j.1600-0463.2002.100110.x

Cited by 65 publications

(60 citation statements)

References 27 publications

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“…In 1996, the National CJD Surveillance Unit in Edinburgh reported 10 patients with a new variant form of CJD, which was subsequently referred to as variant CJD (vCJD) [21]. This disorder was identified on the basis of its clinical and pathological features, which have remained relatively uniform since its original description (Table 4) [22,23]. No significant differences exist in the sex incidence of this disease, but the wide age range (12-74 years at onset) has raised questions concerning the adequacy of disease surveillance in the elderly population, particularly in view of the declining autopsy rate in the UK.…”

Section: Variant Cjdmentioning

confidence: 99%

“…No significant differences exist in the sex incidence of this disease, but the wide age range (12-74 years at onset) has raised questions concerning the adequacy of disease surveillance in the elderly population, particularly in view of the declining autopsy rate in the UK. Pathologically, the disease is characterized by the presence of numerous florid plaques in the cerebral cortex and cerebellum, which are large amyloid plaques composed of PrP Sc , surrounded by spongiform change [23]. In other brain regions, the neuropathological features are variable, but the posterior thalamus consistently shows extensive neural loss and astrocytosis, the distribution of which is reflected in the high signal present in the posterior thalamus in magnetic resonance imaging scans of the brain [24].…”

Section: Variant Cjdmentioning

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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Section: Variant Cjdmentioning

confidence: 99%

Section: Variant Cjdmentioning

confidence: 99%

Variant Creutzfeldt–Jakob disease and its transmission by blood

Ironside

Head

2003

Journal of Thrombosis and Haemostasis

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“…As PrP Sc is abundantly accumulated in the brain, brain samples are appropriate for these detection methods, which require post-mortem analysis. Immunohistochemical (IHC) examination of brain sections is a relatively reliable method of prion diagnosis [3,46] in which typical features of prion diseases, such as accumulation of prion protein (PrP) amyloid plaques, astrogliosis, and neuronal cell loss, are examined by light microscopy. Vacuolation is also used as an index of prion infection.…”

Section: Conventional Diagnostic Methods For Prion Diseasesmentioning

confidence: 99%

Recent Developments in Prion Disease Research: Diagnostic Tools and In Vitro Cell Culture Models

Sakudo

Nakamura

Ikuta

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. After prion infection, an abnormal isoform of prion protein (PrP Sc ) converts the cellular isoform of prion protein (PrP C ) into PrP Sc . PrP C -to-PrP Sc conversion leads to PrP Sc accumulation and PrP C deficiency, contributing etiologically to induction of prion diseases. Presently, most of the diagnostic methods for prion diseases are dependent on PrP Sc detection. Highly sensitive/accurate specific detection of PrP Sc in many different samples is a prerequisite for attempts to develop reliable detection methods. Towards this goal, several methods have recently been developed to facilitate sensitive and precise detection of PrP Sc , namely, protein misfolding cyclic amplification, conformation-dependent immunoassay, dissociation-enhanced lanthanide fluorescent immunoassay, capillary gel electrophoresis, fluorescence correlation spectroscopy, flow microbead immunoassay, etc. Additionally, functionally relevant prion-susceptible cell culture models that recognize the complexity of the mechanisms of prion infection have also been pursued, not only in relation to diagnosis, but also in relation to prion biology. Prion protein (PrP) gene-deficient neuronal cell lines that can clearly elucidate PrP C functions would contribute to understanding of the prion infection mechanism. In this review, we describe the trend in recent development of diagnostic methods and cell culture models for prion diseases and their potential applications in prion biology. Evidence of prion infections has been established by the accumulation of an abnormal isoform of prion protein (PrP Sc ) and/or infectivity after multiple passages [54,85,94,131]. In vitro conversion of the cellular isoform of prion protein (PrP C ) to form PrP Sc -like products has been demonstrated by incubating 35 S-labeled PrP C with PrP Sc . This produced a protease-resistant radioactive product with the mobility of protease-treated authentic PrP Sc [55]. This in vitro conversion confirms the species-[90] and strain-specificities [7] observed in vivo. However, because the yield is less stoichiometric than for PrP Sc [55], it has not been possible to determine whether or not an increase in infectivity occurred [55]. Recent progress in the development of diagnostic methods for PrP Sc detection has dramatically facilitated many approaches in prion biology. The protein misfolding cyclic amplification (PMCA) method deserves special mention [96]. Hitherto, it has not been possible to renature completely denatured prion preparations to an infectious state [79,81]; however, the novel PMCA approach enables in vitro amplification of infectious prions [16].The susceptibility of cell lines, such as N2a, in an in vitro cell culture assay to prion infections has been assessed by exposing the cells to serial dilutions of prion-infected mouse brain homogenates, and the dilution rate yielding negative outcome in a blotting assay for PrP Sc has been determined to be the infectivity level. Prion concentrations equivalent to those determined in an animal bioassay [9] have ...

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“…28 It is believed that vCJD possesses distinct clinical and neuropathological characteristics from sporadic CJD (sCJD) and other forms of prion disease in human. 29 The main distinguishing neuropathological feature of vCJD is an extensive deposition of PrP Sc amyloid in the brain in the form of large 'florid' plaques. 30 Other phenotypes include a younger average age of onset, and gliosis of the thalamis.…”

Section: Types Of Prion Diseasementioning

confidence: 99%

“…Therefore, the UK National CJD Surveillance Unit reported that vCJD is caused by exposure to BSE and that the primary source of exposure is the consumption of infected meat products. 29 Unlike vCJD, Iatrogenic CJD is an entirely person to person transmitted disease, identified to be transmitted through a number of mechanisms including contaminated surgical instruments, 33 and dura mater grafts, 34 blood transfusions 35 and injection of products from cadaveric pituitary glands. 36, 37 The first case of iCJD was described in 1974 where a corneal graft recipient died after acquiring a dementialike likness.…”

Section: Types Of Prion Diseasementioning

confidence: 99%

Prion protein scrapie and the normal cellular prion protein

Atkinson

Zhang

Munn

et al. 2015

Prion

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ABSTRACT. Prions are infectious proteins and over the past few decades, some prions have become renowned for their causative role in several neurodegenerative diseases in animals and humans. Since their discovery, the mechanisms and mode of transmission and molecular structure of prions have begun to be established. There is, however, still much to be elucidated about prion diseases, including the development of potential therapeutic strategies for treatment. The significance of prion disease is discussed here, including the categories of human and animal prion diseases, disease transmission, disease progression and the development of symptoms and potential future strategies for treatment. Furthermore, the structure and function of the normal cellular prion protein (PrP C ) and its importance in not only in prion disease development, but also in diseases such as cancer and Alzheimer's disease will also be discussed.

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Pathological diagnosis of variant Creutzfeldt‐Jakob disease

Cited by 65 publications

References 27 publications

Variant Creutzfeldt–Jakob disease and its transmission by blood

Variant Creutzfeldt–Jakob disease and its transmission by blood

Recent Developments in Prion Disease Research: Diagnostic Tools and In Vitro Cell Culture Models

Prion protein scrapie and the normal cellular prion protein

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