Sporadic Creutzfeldt-Jakob disease in older people

2009 ◽  
Vol 19 (3) ◽  
pp. 207-215
Author(s):  
N Shah ◽  
A Agbobu ◽  
I Costello ◽  
A Beri ◽  
K Minhas
Keyword(s):  
Older People ◽  
Age Of Onset ◽  
Prion Proteins ◽  
Prion Diseases ◽  
Human Prion Disease ◽  
Degenerative Disorders ◽  
Abnormal Accumulation ◽  
Jakob Disease ◽  
The Uk ◽  
Sporadic Cjd

SummaryPrion diseases are rare degenerative disorders of the nervous system caused by abnormal accumulation and/or metabolism of prion proteins. They are invariably fatal. Creutzfeldt-Jakob disease (CJD) is the most common human prion disease and the sporadic form accounts for 85% of cases, whilst about 15% are genetic and 1% is iatrogenic. Variant CJD (vCJD) was mostly seen in the UK and France and mainly affected young people. Sporadic CJD (sCJD) occurs throughout the world with mean age of onset in the seventh decade. It typically presents with rapidly declining cognition that may get confused with other forms of dementia. Thus identification of sCJD in older people depends on a judicious awareness of the clinical features. Here we present a clinical, pathological, therapeutic and diagnostic review of sCJD.

scholarly journals Study protocol for enhanced CJD surveillance in the 65+ years population group in Scotland: an observational neuropathological screening study of banked brain tissue donations for evidence of prion disease

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e033744
Author(s):  
Alexander Howard Peden ◽  
Lovney Kanguru ◽  
Diane L Ritchie ◽  
Colin Smith ◽  
Anna M Molesworth
Keyword(s):  
Brain Tissue ◽  
Prion Disease ◽  
Age Of Onset ◽  
Population Group ◽  
Immunohistochemical Analysis ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Tissue Samples ◽  
Jakob Disease ◽  
The Uk

IntroductionCreutzfeldt-Jakob disease (CJD) is a human prion disease that occurs in sporadic, genetic and acquired forms. Variant CJD (vCJD) is an acquired form first identified in 1996 in the UK. To date, 178 cases of vCJD have been reported in the UK, most of which have been associated with dietary exposure to the bovine spongiform encephalopathy agent. Most vCJD cases have a young age of onset, with a median age at death of 28 years. In the UK, suspected cases of vCJD are reported to the UK National Creutzfeldt-Jakob Disease Research & Surveillance Unit (NCJDRSU). There is, however, a concern that the national surveillance system might be missing some cases of vCJD or other forms of human prion disease, particularly in the older population, perhaps because of atypical clinical presentation. This study aims to establish whether there is unrecognised prion disease in people aged 65 years and above in the Scottish population by screening banked brain tissue donated to the Edinburgh Brain Bank (EBB).MethodsNeuropathological screening of prospective and retrospective brain tissue samples is performed. This involves histopathological and immunohistochemical analysis and prion protein biochemical analysis. During the study, descriptive statistics are used to describe the study population, including the demographics and clinical, pathological and referral characteristics. Controlling for confounders, univariate and multivariate analyses will be used to compare select characteristics of newly identified suspect cases with previously confirmed cases referred to the NCJDRSU.Ethics and disseminationBrain tissue donations to EBB are made voluntarily by the relatives of patients, with consent for use in research. The EBB has ethical approval to provide tissue samples to research projects (REC reference 16/ES/0084). The findings of this study will be disseminated in meetings, conferences, workshops and as peer-reviewed publications.Trial registration numbers10/S1402/69 and 10/S1402/70

The neuroepidemiology of human prion disease

2020 ◽  
pp. 367-378
Author(s):  
Patrick JM Urwin ◽  
Anna M Molesworth
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Human Prion Disease ◽  
Disease States ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Sporadic Disease

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

scholarly journals Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Christina D. Orrú ◽  
Bradley R. Groveman ◽  
Andrew G. Hughson ◽  
Gianluigi Zanusso ◽  
Michael B. Coulthart ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Analytical Sensitivity ◽  
Enhanced Sensitivity ◽  
Highly Sensitive ◽  
Jakob Disease ◽  
Misfolding Diseases ◽  
Amyloid Diseases ◽  
Sporadic Cjd

ABSTRACT  Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis. IMPORTANCE A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer’s, Parkinson’s, and tauopathies.

scholarly journals Risk of Transmissibility From Neurodegenerative Disease-Associated Proteins: Experimental Knowns and Unknowns

2020 ◽  
Vol 79 (11) ◽  
pp. 1141-1146
Author(s):  
David M Asher ◽  
Ermias Belay ◽  
Eileen Bigio ◽  
Sebastian Brandner ◽  
Scott A Brubaker ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Prion Proteins ◽  
Current Knowledge ◽  
Scientific Practice ◽  
Prion Diseases ◽  
Research Priorities ◽  
Neural Systems ◽  
Native Proteins ◽  
Associated Proteins ◽  
Jakob Disease

Abstract Recent studies in animal models demonstrate that certain misfolded proteins associated with neurodegenerative diseases can support templated misfolding of cognate native proteins, to propagate across neural systems, and to therefore have some of the properties of classical prion diseases like Creutzfeldt-Jakob disease. The National Institute of Aging convened a meeting to discuss the implications of these observations for research priorities. A summary of the discussion is presented here, with a focus on limitations of current knowledge, highlighting areas that appear to require further investigation in order to guide scientific practice while minimizing potential exposure or risk in the laboratory setting. The committee concluded that, based on all currently available data, although neurodegenerative disease-associated aggregates of several different non-prion proteins can be propagated from humans to experimental animals, there is currently insufficient evidence to suggest more than a negligible risk, if any, of a direct infectious etiology for the human neurodegenerative disorders defined in part by these proteins. Given the importance of this question, the potential for noninvasive human transmission of proteopathic disorders is deserving of further investigation.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2019

2020 ◽  
Vol 44 ◽  
Author(s):  
Christiane Stehmann ◽  
Matteo Senesi ◽  
Shannon Sarros ◽  
Amelia McGlade ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Annual Number ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of Creutzfeldt-Jakob disease and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2019. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2019, 513 domestic CSF specimens were referred for 14-3-3 protein testing and 85 persons with suspected human prion disease were formally added to the national register. As of 31 December 2019, just under half (42 cases) of the 85 suspect case notifications remain classified as ‘incomplete’; 16 cases were excluded through either detailed clinical follow-up (3 cases) or neuropathological examination (13 cases); 20 cases were classified as ‘definite’ and seven as ‘probable’ prion disease. For 2019, sixty-three percent of all suspected human prion disease related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. Two possibly causal novel prion protein gene (PRNP) sequence variations were identified. Keywords: Creutzfeldt-Jakob disease, prion disease, transmissible spongiform encephalopathy, disease surveillance

scholarly journals Analysis of 22 years of surveillance for prion diseases in Slovenia, 1996 to 2017

2018 ◽  
Vol 57 (4) ◽  
pp. 227-233
Author(s):  
Nuška čakš Jager ◽  
Mara Popović ◽  
Mateja Blaško Markič ◽  
Alenka Kraigher
Keyword(s):  
Public Health ◽  
Prion Diseases ◽  
Interdisciplinary Approach ◽  
Diagnostic Value ◽  
Incidence Rates ◽  
Effective Response ◽  
Jakob Disease ◽  
Reporting Data ◽  
Sporadic Cjd ◽  
Completeness Of Reporting

Abstract Introduction The objective was to present the results of surveillance of prion diseases in Slovenia that was established in 1996 and then to assess the interdisciplinary approach according to the algorithm of case management and reporting data to the National Register at the National Institute of Public Health. Methods A descriptive study of Creutzfeldt-Jakob disease (CJD) recorded in the period from 1996 to 2017 was carried out. Results A total of 123 cases of prion disease were notified between 1996 and 2017. Out of these, 68 were recorded and confirmed by autopsy as sporadic CJD with an average incidence rate of 1,5 cases per million population per year. In one case a gene analysis showed mutation E200K in prion protein gene, PRNP. Two cases of the Gerstman-Sträussler Scheinker syndrome and one clinical case of fatal insomnia with new PRNP mutation, N181S, were notified. Diagnostic value of protein 14-3-3 analysis in the liquor reached 82% sensitivity and 71% specificity. 25 cases of notified clinically possible/probable CJD were disproved after autopsy. In eleven notified possible CJD cases the autopsy had not been performed. Variant CJD has not yet been proven in Slovenia. Conclusion Incidence rates were comparable with other European countries. Completeness of reporting and proper management of CJD cases according to the algorithm of reporting, management and case confirmation would need some improvement. A well-functioning surveillance system, including timely notifications, would enable an appropriate epidemiological investigation and an effective response to public health risks, thus the awareness of prion diseases should not decline.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2018

2019 ◽  
Vol 43 ◽  
Author(s):  
Christine Stehmann ◽  
Matteo Senesi ◽  
Victoria Lewis ◽  
Mairin Ummi ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Annual Number ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Surveillance Period ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of human prion diseases (also known as transmissible spongiform encephalopathies), the most common being Creutzfeldt-Jakob disease (CJD), is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR), based at the University of Melbourne. National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period considerable developments have occurred in relation to pre-mortem diagnostics, the delineation of new disease subtypes and a heightened awareness of prion diseases in health care settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR from 1 January to 31 December 2018. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2018, 465 domestic CSF specimens were referred for 14-3-3 protein testing and 78 persons with suspected human prion disease were formally added to the national register. The majority of the 78 suspect case notifications remain as of 31 December 2018 classified as “incomplete” (42 cases), while eleven cases were excluded by either detailed clinical follow-up (one case) or neuropathological examination (ten cases); 15 cases were classified as “definite” and ten as “probable” prion disease. Sixty-two percent of all suspected human prion disease related deaths underwent neuropathological examination. No cases of variant CJD were confirmed.

scholarly journals Three serial passages of bovine spongiform encephalopathy in sheep do not significantly affect discriminatory test results

2009 ◽  
Vol 90 (3) ◽  
pp. 764-768 ◽  
Author(s):  
Michael Stack ◽  
Lorenzo González ◽  
Martin Jeffrey ◽  
Stuart Martin ◽  
Colin Macaldowie ◽  
...  
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Proteins ◽  
Oral Exposure ◽  
Spongiform Encephalopathy ◽  
Test Results ◽  
Western Immunoblotting ◽  
Jakob Disease ◽  
Disease Variant ◽  
The Uk ◽  
Sheep Scrapie

During the 1980s, bovine spongiform encephalopathy (BSE)-contaminated meat and bonemeal were probably fed to sheep, raising concerns that BSE may have been transmitted to sheep in the UK. The human disease, variant Creutzfeldt–Jakob disease, arose during the BSE epidemic, and oral exposure of humans to BSE-infected tissues has been implicated in its aetiology. The concern is that sheep BSE could provide another source of BSE exposure to humans via sheep products. Two immunological techniques, Western immunoblotting (WB) and immunohistochemistry (IHC), have been developed to distinguish scrapie from cases of experimental sheep BSE by the characteristics of their respective abnormal, disease-associated prion proteins (PrPd). This study compares the WB and IHC characteristics of PrPd from brains of primary, secondary and tertiary experimental ovine BSE cases with those of cattle BSE and natural sheep scrapie. Discrimination between experimental sheep BSE and scrapie remained possible by both methods, regardless of the route of challenge.

scholarly journals MicroRNAs in Prion Diseases—From Molecular Mechanisms to Insights in Translational Medicine

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1620
Author(s):  
Danyel Fernandes Contiliani ◽  
Yasmin de Araújo Ribeiro ◽  
Vitor Nolasco de Moraes ◽  
Tiago Campos Pereira
Keyword(s):  
Molecular Mechanisms ◽  
Prion Proteins ◽  
Prion Diseases ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Non Invasive ◽  
Non Coding Rna ◽  
Jakob Disease ◽  
Health And Disease ◽  
Interesting Alternative

MicroRNAs (miRNAs) are small non-coding RNA molecules able to post-transcriptionally regulate gene expression via base-pairing with partially complementary sequences of target transcripts. Prion diseases comprise a singular group of neurodegenerative conditions caused by endogenous, misfolded pathogenic (prion) proteins, associated with molecular aggregates. In humans, classical prion diseases include Creutzfeldt–Jakob disease, fatal familial insomnia, Gerstmann–Sträussler–Scheinker syndrome, and kuru. The aim of this review is to present the connections between miRNAs and prions, exploring how the interaction of both molecular actors may help understand the susceptibility, onset, progression, and pathological findings typical of such disorders, as well as the interface with some prion-like disorders, such as Alzheimer’s. Additionally, due to the inter-regulation of prions and miRNAs in health and disease, potential biomarkers for non-invasive miRNA-based diagnostics, as well as possible miRNA-based therapies to restore the levels of deregulated miRNAs on prion diseases, are also discussed. Since a cure or effective treatment for prion disorders still pose challenges, miRNA-based therapies emerge as an interesting alternative strategy to tackle such defying medical conditions.

scholarly journals A field on fire: The biochemistry of mad cows

2005 ◽  
Vol 27 (4) ◽  
pp. 6-8
Author(s):  
David R. Brown
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Human Diseases ◽  
Spongiform Encephalopathy ◽  
Related Disease ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are neurodegenerative diseases1 that have been linked together because they may potentially have the same cause. These include the diseases scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and also several human diseases that include sporadic CJD (Creutzfeldt-Jakob) disease and a variety of inherited forms. The inherited forms of prion diseases are linked to mutations within the gene for the prion protein. Around 85% of all human cases of prion disease are sporadic CJD, which is a disease affecting people of around 60 years of age. The cause of this disease remains unknown. Unfortunately, the name of this disease causes some confusion, as it is similar to vCJD (variant CJD), a related disease of much younger people.

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