Human prion diseases

Distinct Disease ◽

Jakob Disease ◽

Disease Variant

Prion protein (for proteinacious infectious particle) is a membrane-associated glycoprotein present in all mammalian species. Its normal function is unknown, but in prion diseases (also known as transmissible spongiform encephalopathies) a misfolded polymer form of the protein, partially resistant to protease digestion, is deposited in the brain and associated—typically after long incubation periods—with neuronal dysfunction and death. Prion diseases have become the subject of intense scientific and public interest because they are caused by a biologically distinct disease mechanism and because of the implications for public health following the identification of a new human prion disease, variant Creutzfeldt–Jakob disease (vCJD), and the evidence that it is caused by the transmission to humans of a cattle prion disease, bovine spongiform encephalopathy (BSE).

Creutzfeldt–Jakob disease surveillance in Australia: update to December 2017

Communicable Diseases Intelligence ◽

10.33321/cdi.2019.43.32 ◽

2019 ◽

Vol 43 ◽

Cited By ~ 1

Author(s):

Christiane Stehmann ◽

Shannon Sarros ◽

Matteo Senesi ◽

Victoria Lewis ◽

Marion Simpson ◽

...

Keyword(s):

Prion Disease ◽

Disease Surveillance ◽

Prion Diseases ◽

Annual Number ◽

Prospective Surveillance ◽

Surveillance Period ◽

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 1970, with prospective surveillance occurring from 1993 onwards. Over this prospective surveillance period considerable developments have occurred, especially in relation to pre-mortem diagnostics, the delineation of new disease subtypes and a heightened awareness of prion diseases in the health care setting. The surveillance practices of the ANCJDR have evolved and adapted accordingly. Since the ANCJDR began offering cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased to a maximum of 508 in 2017. The number of CSF test referrals in 2017 represents a 20% increase compared to that of 2016. In 2017, there was an overall stabilisation of the annual incidence rate of confirmed prion disease in Australia at expected levels; 72 persons with suspected human prion disease were added to the national register, with 72% of all suspected CJD cases undergoing neuropathological examination. The majority of the 72 suspected cases added to the register are as of 31 December 2017 still classified as “incomplete” (47 cases), while four cases were excluded by either detailed clinical follow-up (1 case) or neuropathological examination (3 cases); 19 cases were classified as definite and two as probable prion disease. No cases of variant CJD (vCJD) were confirmed.

Prion disease: advances in diagnosis and treatment

Morecambe Bay Medical Journal ◽

10.48037/mbmj.v4i10.877 ◽

2005 ◽

Vol 4 (10) ◽

pp. 273-278

Author(s):

Steve Dealler

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Prion Disease ◽

The Political ◽

Potential Treatment ◽

Current State ◽

Jakob Disease ◽

Pentosan Polysulphate

Steve Dealler is a medical microbiologist with Morecambe Bay Hospitals NHS Trust. His work on on the diagnosis, epidemiology and potential treatment of transmissible spongiform encephalopathies has brought him inter-national recognition. He has been at the forefront of work on the epidemiology of human food containing the vector for bovine spongiform encephalopathy (BSE), and the development of prophylaxis against variant Creutzfeldt-Jakob disease (vCJD). He is currently working on a potential treatment, pentosan polysulphate. Here he describes the current state of knowledge in the battle against this devastating disease and the political inertia that frustrated earlier attempts to prevent the epidemic.

Human Prion Diseases

Escourolle and Poirier's Manual of Basic Neuropathology ◽

10.1093/med/9780199929054.003.0006 ◽

2013 ◽

pp. 149-160

Author(s):

James W. Ironside ◽

Matthew P. Frosch ◽

Bernardino Ghetti

Keyword(s):

Prion Diseases ◽

Neuronal Loss ◽

Pituitary Hormone ◽

Human Pituitary ◽

Jakob Disease ◽

Prnp Codon ◽

Codon 129

This chapter describes and illustrates the neuropathology of prion diseases, also known as transmissible spongiform encephalopathies. These diseases are characterized pathologically by varying combinations of spongiform change, neuronal loss, reactive gliosis, and prion protein (PrP) deposition. The morphologic pattern depends on the etiology of the disease and the genotype of the patient. Different clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (CJD) have been described depending on the PRNP codon 129 genotype and the PrP isotype. A novel form known as variably protease-sensitive prionopathy has been recently identified. Familial prion diseases include familial CJD, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Over 40 different PRNP mutations have been identified. Acquired prion diseases include Kuru; iatrogenic CJD, particularly in recipients of contaminated human pituitary hormone, and variant CJD, which seems closely related to bovine spongiform encephalopathy.

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

Communicable Diseases Intelligence ◽

10.33321/cdi.2019.43.35 ◽

2019 ◽

Vol 43 ◽

Cited By ~ 2

Author(s):

Christine Stehmann ◽

Matteo Senesi ◽

Victoria Lewis ◽

Mairin Ummi ◽

Marion Simpson ◽

...

Keyword(s):

Prion Disease ◽

Prion Diseases ◽

Annual Number ◽

Human Prion Disease ◽

Prospective Surveillance ◽

Surveillance Period ◽

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.

Detection and Control of Prion Diseases in Food Animals

ISRN Veterinary Science ◽

10.5402/2012/254739 ◽

2012 ◽

Vol 2012 ◽

pp. 1-24 ◽

Cited By ~ 7

Author(s):

Peter Hedlin ◽

Ryan Taschuk ◽

Andrew Potter ◽

Philip Griebel ◽

Scott Napper

Keyword(s):

Prion Disease ◽

Disease Transmission ◽

Management Practices ◽

Prion Diseases ◽

Case Scenario ◽

Worst Case ◽

Food Animals

Transmissible spongiform encephalopathies (TSEs), or prion diseases, represent a unique form of infectious disease based on misfolding of a self-protein (PrPC) into a pathological, infectious conformation (PrPSc). Prion diseases of food animals gained notoriety during the bovine spongiform encephalopathy (BSE) outbreak of the 1980s. In particular, disease transmission to humans, to the generation of a fatal, untreatable disease, elevated the perspective on livestock prion diseases from food production to food safety. While the immediate threat posed by BSE has been successfully addressed through surveillance and improved management practices, another prion disease is rapidly spreading. Chronic wasting disease (CWD), a prion disease of cervids, has been confirmed in wild and captive populations with devastating impact on the farmed cervid industries. Furthermore, the unabated spread of this disease through wild populations threatens a natural resource that is a source of considerable economic benefit and national pride. In a worst-case scenario, CWD may represent a zoonotic threat either through direct transmission via consumption of infected cervids or through a secondary food animal, such as cattle. This has energized efforts to understand prion diseases as well as to develop tools for disease detection, prevention, and management. Progress in each of these areas is discussed.

Prion diseases: Update on mad cow disease, variant creutzfeldt-jakob disease, and the transmissible spongiform encephalopathies

Current Infectious Disease Reports ◽

10.1007/s11908-004-0053-y ◽

2004 ◽

Vol 6 (4) ◽

pp. 305-315 ◽

Cited By ~ 8

Author(s):

Jacqueline Janka ◽

Frank Maldarelli

Keyword(s):

Prion Diseases ◽

Jakob Disease ◽

Mad Cow Disease ◽

Disease Variant

Reduced SOD2 expression does not influence prion disease course or pathology in mice

PLoS ONE ◽

10.1371/journal.pone.0259597 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259597

Author(s):

Simote T. Foliaki ◽

Brent Race ◽

Katie Williams ◽

Chase Baune ◽

Bradley R. Groveman ◽

...

Keyword(s):

Prion Disease ◽

Prion Diseases ◽

Critical Role ◽

Long Term Potentiation ◽

Knock Out ◽

Spongiform Change ◽

Knock Out Mice

Prion diseases are progressive, neurodegenerative diseases affecting humans and animals. Also known as the transmissible spongiform encephalopathies, for the hallmark spongiform change seen in the brain, these diseases manifest increased oxidative damage early in disease and changes in antioxidant enzymes in terminal brain tissue. Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that is critical for life. SOD2 knock-out mice can only be kept alive for several weeks post-birth and only with antioxidant therapy. However, this results in the development of a spongiform encephalopathy. Consequently, we hypothesized that reduced levels of SOD2 may accelerate prion disease progression and play a critical role in the formation of spongiform change. Using SOD2 heterozygous knock-out and litter mate wild-type controls, we examined neuronal long-term potentiation, disease duration, pathology, and degree of spongiform change in mice infected with three strains of mouse adapted scrapie. No influence of the reduced SOD2 expression was observed in any parameter measured for any strain. We conclude that changes relating to SOD2 during prion disease are most likely secondary to the disease processes causing toxicity and do not influence the development of spongiform pathology.

The molecular biology of prion propagation

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2000.0764 ◽

2001 ◽

Vol 356 (1406) ◽

pp. 185-195 ◽

Cited By ~ 31

Author(s):

Anthony R. Clarke ◽

Graham S. Jackson ◽

John Collinge

Keyword(s):

Prion Diseases ◽

Mammalian Species ◽

Infectious Agent ◽

Conformational Isomer ◽

Prion Propagation ◽

Jakob Disease ◽

Fundamental Biology ◽

Disease Variant

Prion diseases such as Creutzfeldt–Jakob disease (CJD) in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals are associated with the accumulation in affected brains of a conformational isomer (PrP Sc ) of host–derived prion protein (PrP C ). According to the protein–only hypothesis, PrP Sc is the principal or sole component of transmissible prions. The conformational change known to be central to prion propagation, from a predominantly α–helical fold to one predominantly comprising β structure, can now be reproduced in vitro , and the ability of β–PrP to form fibrillar aggregates provides a plausible molecular mechanism for prion propagation. The existence of multiple prion strains has been difficult to explain in terms of a protein–only infectious agent but recent studies of human prion diseases suggest that strain–specific phenotypes can be encoded by different PrP conformations and glycosylation patterns. The experimental confirmation that a novel form of human prion disease, variant CJD, is caused by the same prion strain as cattle BSE, has highlighted the pressing need to understand the molecular basis of prion propagation and the transmission barriers that limit their passage between mammalian species. These and other advances in the fundamental biology of prion propagation are leading to strategies for the development of rational therapeutics.

Making blood safe: A filtration technology for removing infectious prions from red-cell concentrates

The Biochemist ◽

10.1042/bio02704029 ◽

2005 ◽

Vol 27 (4) ◽

pp. 29-32

Author(s):

S.O. Sowemimo-Coker

Keyword(s):

Blood Transfusion ◽

Neurodegenerative Diseases ◽

Bovine Spongiform Encephalopathy ◽

Prion Diseases ◽

Red Cell ◽

Jakob Disease ◽

Filtration Technology

Prion diseases (TSEs, transmissible spongiform encephalopathies) are fatal neurodegenerative diseases that affect both humans and animals, including scrapie in sheep, BSE (bovine spongiform encephalopathy) in cattle and CJD (Creutzfeldt–Jakob disease) and its variant (vCJD) in humans. The recent occurrences of probable cases of transmission of vCJD through blood transfusion raises concerns about the safety of the blood supply and the possibility of transmission of the causative agent by blood transfusion from asymptomatic infected individuals.

An overview of transmissible spongiform encephalopathies

Animal Health Research Reviews ◽

10.1079/ahr200494 ◽

2004 ◽

Vol 5 (2) ◽

pp. 103-124 ◽

Cited By ~ 7

Author(s):

K. Takemura ◽

M. Kahdre ◽

D. Joseph ◽

A. Yousef ◽

S. Sreevatsan

Keyword(s):

Prion Diseases ◽

Infectious Agent ◽

Causal Mechanism ◽

Disease Diagnostics ◽

New Variant ◽

Jakob Disease ◽

Underlying Mechanisms

AbstractTransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders of humans and animals associated with an accumulation of abnormal isoforms of prion protein (PrP) in nerve cells. The pathogenesis of TSEs involves conformational conversions of normal cellular PrP (PrPc) to abnormal isoforms of PrP (PrPSc). While the protein-only hypothesis has been widely accepted as a causal mechanism of prion diseases, evidence from more recent research suggests a possible involvement of other cellular component(s) or as yet undefined infectious agent(s) in PrP pathogenesis. Although the underlying mechanisms of PrP strain variation and the determinants of interspecies transmissibility have not been fully elucidated, biochemical and molecular findings indicate that bovine spongiform encephalopathy in cattle and new-variant Creutzfeldt–Jakob disease in humans are caused by indistinguishable etiological agent(s). Cumulative evidence suggests that there may be risks of humans acquiring TSEs via a variety of exposures to infected material. The development of highly precise ligands is warranted to detect and differentiate strains, allelic variants and infectious isoforms of these PrPs. This article describes the general features of TSEs and PrP, the current understanding of their pathogenesis, recent advances in prion disease diagnostics, and PrP inactivation.