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Mol Neurobiol 2019 Jan 31. Epub 2019 Jan 31.

Russian Academy of Medical Sciences, Moscow, 113152, Russia.

With continuing cooperation from 18 domestic and international brain banks over the last 36 years, we have analyzed the aluminum content of the temporal lobe neocortex of 511 high-quality human female brain samples from 16 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Temporal lobes (Brodmann areas A20-A22) were selected for analysis because of their availability and their central role in massive information-processing operations including efferent-signal integration, cognition, and memory formation. We used the analytical technique of (i) Zeeman-type electrothermal atomic absorption spectrophotometry (ETAAS) combined with (ii) preliminary analysis from the advanced photon source (APS) hard X-ray beam (7 GeV) fluorescence raster-scanning (XRFR) spectroscopy device (undulator beam line 2-ID-E) at the Argonne National Laboratory, US Department of Energy, University of Chicago IL, USA. Read More

Brain Pathol 2018 Dec 26. Epub 2018 Dec 26.

UMR INRA ENVT 1225- IHAP, École Nationale Vétérinaire de Toulouse, Toulouse, France.

Transmissible spongiform encephalopathies (TSEs) or prion diseases of animals notably include scrapie in small ruminants, chronic wasting disease (CWD) in cervids and classical bovine spongiform encephalopathy (C-BSE). As the transmission barrier phenomenon naturally limits the propagation of prions from one species to another, and the lack of epidemiological evidence for an association with human prion diseases, the zoonotic potential of these diseases was for a long time considered negligible. However, in 1996, C-BSE was recognized as the cause of a new human prion disease, variant Creutzfeldt-Jakob disease (vCJD), which triggered an unprecedented public health crisis in Europe. Read More

PLoS Pathog 2018 11 29;14(11):e1007424. Epub 2018 Nov 29.

Institute of Neuropathology, University Hospital Zürich, Zürich University, Zürich, Switzerland.

Transmissible spongiform encephalopathies (TSEs) are caused by the prion, which consists essentially of PrPSc, an aggregated, conformationally modified form of the cellular prion protein (PrPC). Although TSEs can be experimentally transmitted by intracerebral inoculation, most instances of infection in the field occur through extracerebral routes. The epidemics of kuru and variant Creutzfeldt-Jakob disease were caused by dietary exposure to prions, and parenteral administration of prion-contaminated hormones has caused hundreds of iatrogenic TSEs. Read More

Prion 2018 24;12(5-6):301-309. Epub 2018 Oct 24.

a United States Department of Agriculture , Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit , Ames , Iowa , USA.

Propagation of transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrP, into a misfolded oligomeric form, PrP. The most common hereditary prion disease is a genetic form of Creutzfeldt-Jakob disease in humans, in which a mutation in the prion gene results in a glutamic acid to lysine substitution at position 200 (E200K) in PrP. In cattle, the analogous amino acid substitution is found at residue 211 (E211K) and has been associated with a case of bovine spongiform encephalopathy. Read More

Prion 2018 9;12(5-6):280-300. Epub 2018 Oct 9.

a Department of Biological Sciences , University of Alberta , Edmonton , Canada.

Prion diseases are caused by the conversion of normal cellular prion proteins (PrP) into lethal prion aggregates. These prion aggregates are composed of proteinase K (PK) resistant fibrils and comparatively PK-sensitive oligomers. Currently there are no anti-prion pharmaceuticals available to treat or prevent prion disease. Read More

PLoS One 2018 5;13(7):e0199914. Epub 2018 Jul 5.

Centro de Encefalopatías y Enfermedades Transmisibles Emergentes (CEETE), Veterinary Faculty, Universidad de Zaragoza, Zaragoza, Spain.

Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to pigs via intracerebral inoculation. A clear link has been established between the consumption of products of bovine origin contaminated with the BSE agent and the development of variant Creutzfeldt-Jakob disease in humans. Small ruminants can also naturally develop BSE, and sheep-adapted BSE (Sh-BSE) propagates more efficiently than cattle BSE in pigs and in mouse models expressing porcine prion protein. Read More

Handb Clin Neurol 2018 ;153:447-462

École Nationale Vétérinaire de Toulouse, Toulouse, France.

Bovine spongiform encephalopathy (BSE) is the only animal prion disease that has been demonstrated to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans. The link between BSE and vCJD was established by careful surveillance, epidemiologic investigations, and experimental studies using in vivo and in vitro models of cross-species transmission. Similar approaches have been used to assess the zoonotic potential of other animal prion diseases, including atypical forms identified through active surveillance. Read More

Handb Clin Neurol 2018 ;153:419-430

Center for Cognitive Neurology, New York University School of Medicine, New York, NY, United States; Department of Neurology, New York University School of Medicine, New York, NY, United States.

Currently all prion diseases are without effective treatment and are universally fatal. It is increasingly being recognized that the pathogenesis of many neurodegenerative diseases, such as Alzheimer disease (AD), includes "prion-like" properties. Hence, any effective therapeutic intervention for prion disease could have significant implications for other neurodegenerative diseases. Read More

Handb Clin Neurol 2018 ;153:191-205

National CJD Research and Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom. Electronic address:

Variant CJD (vCJD) was described first in the United Kingdom in 1996. It is a zoonotic form of human prion disease, originating from dietary contamination of human food with material from bovine spongiform encephalopathy (BSE)-affected cattle. It has important epidemiologic, clinical, and neuropathogic differences from other forms of human prion disease. Read More

Handb Clin Neurol 2018 ;153:135-151

Prion Research Center (PRC) and the Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, United States. Electronic address:

Chronic wasting disease (CWD) is a relatively new and burgeoning prion epidemic of deer, elk, reindeer, and moose, which are members of the cervid family. While the disease was first described in captive deer, its subsequent discovery in various species of free-ranging animals makes it the only currently recognized prion disorder of both wild and farmed animals. In addition to its expanding range of host species, CWD continues to spread from North America to new geographic areas, including South Korea, and most recently Norway, marking the first time this disease was detected in Europe. Read More

Handb Clin Neurol 2018 ;153:121-134

One Health, Norwich, Norfolk, United Kingdom. Electronic address:

This chapter describes the prion diseases of cattle, or bovine transmissible spongiform encephalopathies (BoTSEs). "Classic" bovine spongiform encephalopathy (C-BSE), the major prion protein disorder of Bovidae, was first described in 1986. We also describe the spatiotemporal correlation of C-BSE to a novel form of human prion disease, variant Creutzfeldt-Jakob disease (vCJD), which led to the classification of BSE as a zoonotic disease (and the "cause" of vCJD) in 1996. Read More

Handb Clin Neurol 2018 ;153:1-17

Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, Division of Emerging and Transfusion-Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, United States.

The first of several pivotal moments leading to current understanding of human transmissible spongiform encephalopathies (TSEs) occurred in 1959 when veterinary pathologist W.J. Hadlow first recognized several similarities between scrapie-a slow infection of sheep caused by an unusual infectious agent-and kuru, a fatal exotic neurodegenerative disease affecting only people of a single language group in the remote mountainous interior of New Guinea, described two years earlier by D. Read More

J Pathol Clin Res 2018 Apr 5;4(2):86-92. Epub 2018 Feb 5.

National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, Deanery of Clinical Medicine, The University of Edinburgh, Edinburgh, UK.

Human prion diseases constitute a group of infectious and invariably fatal neurodegenerative disorders associated with misfolding of the prion protein. Variant Creutzfeldt-Jakob disease (vCJD) is a zoonotic prion disease linked to oral exposure to the infectious agent that causes bovine spongiform encephalopathy (BSE) in cattle. The most recent case of definite vCJD was heterozygous (MV) at polymorphic codon 129 of the prion protein gene PRNP while all of the previous 177 definite or probable vCJD cases who underwent genetic analysis were methionine homozygous (MM). Read More

J Gen Virol 2018 Feb 1. Epub 2018 Feb 1.

1​U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Blood Research and Review, Department of Emerging and Transfusion Transmitted Diseases, Laboratory of Bacterial and Transmissible Spongiform Encephalopathy Agents, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

Transmissible spongiform encephalopathies (TSEs) are infections that are experimentally transmissible to laboratory animals. TSE agents (prions) can be serially passaged in the same animal species. The susceptibility of mice to infection with specific TSE agents can be unpredictable and must be established empirically. Read More

Pathogens 2018 Feb 7;7(1). Epub 2018 Feb 7.

CIMUS Biomedical Research Institute & Department of Medical Sciences, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain.

PrP (scrapie isoform of the prion protein) prions are the infectious agent behind diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (deer, elk, moose, and reindeer), as well as goat and sheep scrapie. PrP is an alternatively folded variant of the cellular prion protein, PrP, which is a regular, GPI-anchored protein that is present on the cell surface of neurons and other cell types. While the structure of PrP is well studied, the structure of PrP resisted high-resolution determination due to its general insolubility and propensity to aggregate. Read More

J Neurol Sci 2018 03 29;386:4-11. Epub 2017 Dec 29.

MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, UK. Electronic address:

The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), causes variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. While it is assumed that all cases of vCJD attributed to a dietary aetiology are related to cattle BSE, sheep and goats are susceptible to experimental oral challenge with cattle BSE prions and farmed animals in the UK were undoubtedly exposed to BSE-contaminated meat and bone meal during the late 1980s and early 1990s. Although no natural field cases of sheep BSE have been identified, it cannot be excluded that some BSE-infected sheep might have entered the European human food chain. Read More

Vox Sang 2018 Apr 22;113(3):220-231. Epub 2018 Jan 22.

The Plasma Protein Therapeutics Association (PPTA), Annapolis, MD, USA.

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Read More

Acta Neuropathol Commun 2018 01 8;6(1). Epub 2018 Jan 8.

Departments of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.

The presence of pathology related to the deposition of amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP with the exception of iCJD harboring the "MMi" phenotype. Read More

BMC Res Notes 2017 Dec 20;10(1):759. Epub 2017 Dec 20.

United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, IA, USA.

Objective: The most common hereditary prion disease is human Creutzfeldt-Jakob disease (CJD), associated with a mutation in the prion gene resulting in a glutamic acid to lysine substitution at position 200 (E200K) in the prion protein. Models of E200K CJD in transgenic mice have proven interesting but have limitations including inconsistencies in disease presentation, requirement for mixed species chimeric protein constructs, and the relatively short life span and time to disease onset in rodents. These factors limit research on the mechanism by which the mutation drives disease development. Read More

Prion 2018 01 2;12(1):34-41. Epub 2018 Jan 2.

a State Key Laboratory for Infectious Disease Prevention and Control , Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing , People's Republic of China.

Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. Besides of the pathological agent, prion, there are some elements that can influence or determine susceptibility to prion infection and the clinical phenotype of the diseases, e.g. Read More

Nat Commun 2017 11 2;8(1):1268. Epub 2017 Nov 2.

CEA, Institut François Jacob, Université Paris-Saclay, 18 Route du Panorama, 92265, Fontenay-aux-Roses, France.

Exposure of human populations to bovine spongiform encephalopathy through contaminated food has resulted in <250 cases of variant Creutzfeldt-Jakob disease (vCJD). However, more than 99% of vCJD infections could have remained silent suggesting a long-term risk of secondary transmission particularly through blood. Here, we present experimental evidence that transfusion in mice and non-human primates of blood products from symptomatic and non-symptomatic infected donors induces not only vCJD, but also a different class of neurological impairments. Read More

Methods Mol Biol 2017 ;1658:311-346

MRC Prion Unit at UCL, UCL Institute of Prion Diseases, Queen Square, London, WC1N 3BG, UK.

Human prion diseases are associated with a range of clinical presentations, and they are classified by both clinicopathological syndrome and etiology, with subclassification according to molecular criteria. Here, we describe updated procedures that are currently used within the MRC Prion Unit at UCL to determine a molecular diagnosis of human prion disease. Sequencing of the PRNP open reading frame to establish the presence of pathogenic mutations is described, together with detailed methods for immunoblot or immunohistochemical determination of the presence of abnormal prion protein in the brain or peripheral tissues. Read More

Methods Mol Biol 2017 ;1658:219-252

Cell and Molecular Biology Graduate Program, Molecular, Cellular and Integrative Neuroscience Graduate Program, Department of Microbiology, Immunology and Pathology, Prion Research Center, Colorado State University, Fort Collins, CO, 80523, USA.

Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSEs), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrP) by the pathogenic isoform (PrP) that is the basis of prion formation in TSEs is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer's and Parkinson's diseases. Read More

Prog Mol Biol Transl Sci 2017 14;150:293-318. Epub 2017 Aug 14.

National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom. Electronic address:

Prion diseases are progressive fatal encephalopathies characterized by a neurodegenerative pathology, the tissue deposition of abnormally folded prion protein and, in general, potential transmissibility. Creutzfeldt-Jakob disease (CJD) is the commonest human prion disease and occurs in three principal forms: sporadic (idiopathic), acquired (infectious), and inherited (genetic). This chapter concerns the sporadic and acquired forms. Read More

Prog Mol Biol Transl Sci 2017 7;150:181-201. Epub 2017 Aug 7.

Centro de Investigación en Sanidad Animal, CISA-INIA, Madrid, Spain. Electronic address:

Transmissible spongiform encephalopathies (TSEs) are a group of progressive, invariably fatal diseases that affect the nervous system of many mammals including humans. The key molecular event in the pathogenesis of TSEs is the conversion of the cellular prion protein PrP into a disease-associated isoform PrP. The "protein-only hypothesis" argues that PrP itself is the infectious agent. Read More

Emerg Infect Dis 2017 09;23(9):1593-1596

We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date. Read More

Emerg Infect Dis 2017 09;23(9):1522-1530

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met) or valine (Val) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Read More

Adv Neurobiol 2017 ;15:335-364

Department of Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia.

Prion diseases are a group of invariably fatal and transmissible neurodegenerative disorders that are associated with the misfolding of the normal cellular prion protein, with the misfolded conformers constituting an infectious unit referred to as a "prion". Prions can spread within an affected organism by directly propagating this misfolding within and between cells and can transmit disease between animals of the same and different species. Prion diseases have a range of clinical phenotypes in humans and animals, with a principle determinant of this attributed to different conformations of the misfolded protein, referred to as prion strains. Read More

J Alzheimers Dis 2017 ;59(1):329-337

Department of Neurology, University Medical School, Georg-August University Göttingen, Germany.

Background: The polymorphism at codon 129 of the prion protein gene (PRNP) and the PrPSc types 1 and 2 belong to a molecular classification of sporadic Creutzfeldt-Jakob disease (sCJD) that correlates well with the clinical and neuropathological phenotype of sCJD.

Objective: The aim of the study was to perform the first detailed evaluation of neuropsychological deficits in a large group of definite sCJD patients with known molecular subtype.

Methods: We analyzed neuropsychological symptoms in a cohort of 248 sCJD patients with known M129 V polymorphism of PRNP and prion protein type. Read More

Neurol Sci 2017 08 25;38(8):1535-1537. Epub 2017 Apr 25.

Department of Neuroscience (DNS), University of Padova, Via Giustiniani 5, 35128, Padova, Italy.

Prion 2017 Mar 30;11(2):113-127. Epub 2017 Mar 30.

c Department of Pathology , National Institute of Infectious Diseases , Shinjuku-ku , Tokyo , Japan.

A classical type of bovine spongiform encephalopathy (C-BSE), recognized in 1987, had a large impact on public health due to its zoonotic link to variant Creutzfeldt-Jakob disease by the human consumption of dietary products contaminated with the C-BSE prion. Thus, a number of countries implemented BSE surveillance using rapid post-mortem test kits that were approved for detection of the C-BSE prion in the cattle brain. However, as atypical BSE (L- and H-BSE) cases emerged in subsequent years, the efficacy of the kits for the detection of atypical BSE prions became a matter of concern. Read More

Transfusion 2017 04 5;57(4):924-932. Epub 2017 Mar 5.

US Food and Drug Administration, Silver Spring, Maryland.

Background: Variant Creutzfeldt-Jakob disease (vCJD) has been transmitted by blood transfusion (TTvCJD). The US Food and Drug Administration (FDA) recommends deferring blood donors who resided in or traveled to 30 European countries where they may have been exposed to bovine spongiform encephalopathy (BSE) through beef consumption. Those recommendations warrant re-evaluation, because new cases of BSE and vCJD have markedly abated. Read More

PLoS One 2017 23;12(2):e0172428. Epub 2017 Feb 23.

Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.

The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Read More

Cold Spring Harb Perspect Med 2018 06 1;8(6). Epub 2018 Jun 1.

Prion Research Center (PRC) and the Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80525.

Prion disease epidemics, which have been unpredictable recurrences, are of significant concern for animal and human health. Examples include kuru, once the leading cause of death among the Fore people in Papua New Guinea and caused by mortuary feasting; bovine spongiform encephalopathy (BSE) and its subsequent transmission to humans in the form of variant Creutzfeldt-Jakob disease (vCJD), and repeated examples of large-scale prion disease epidemics in animals caused by contaminated vaccines. The etiology of chronic wasting disease (CWD), a relatively new and burgeoning prion epidemic in deer, elk, and moose (members of the cervid family), is more enigmatic. Read More

AAPS J 2017 05 23;19(3):765-771. Epub 2017 Jan 23.

Food and Drug Administration, 10903 New Hampshire Avenue, Building 52/72, Room 4336, Silver Spring, Maryland, 20993, USA.

In 2000, bovine heparin was withdrawn from the US market for fear of contamination with bovine spongiform encephalopathy (BSE) agent, the cause of variant Creutzfeldt-Jakob disease in humans. Thus, US heparin is currently sourced only from pig intestines. Availability of alternative sources of crude heparin, a life-saving drug, would benefit public health. Read More

Sci Transl Med 2016 12;8(370):370ra183

Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Houston Medical School, Houston, TX 77030, USA.

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrP) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. Read More

Sci Transl Med 2016 12;8(370):370ra182

Etablissement Français du Sang, INSERM, Université de Montpellier, UMR 1058, TransDiag, F-34184 Montpellier, France.

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. Read More

Trop Anim Health Prod 2017 Feb 8;49(2):427-430. Epub 2016 Nov 8.

Department of Biology, Faculty of Science, Ege University, İzmir, Turkey.

Bovine spongiform encephalopathy (BSE) of the cattle is the outstanding disease among other transmissible spongiform encephalopathy (TSEs). It can be transmitted from the cattle to a human and causes a new variant of the Creutzfeldt-Jakob disease (CJD). It is known that prion protein coding gene (PRNP) plays a major role in the TSE susceptibility or resistance in some species. Read More

Neurol Res 2017 Jan 3;39(1):73-82. Epub 2016 Nov 3.

a Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology , Federal University of Piauí (UFPI) , Teresina , Brazil.

Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Read More

J Virol 2016 Dec 14;90(23):10867-10874. Epub 2016 Nov 14.

VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France

Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP) and the infecting pathological PrP assemblies (PrP) constituting the prion. Read More

Brain 2016 10;139(Pt 10):2609-2616

6 Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. Read More

PLoS Pathog 2016 09 8;12(9):e1005835. Epub 2016 Sep 8.

Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.

The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC) into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. Read More

J Virol 2016 11 14;90(21):9558-9569. Epub 2016 Oct 14.

Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California, USA Department of Neurology, University of California, San Francisco, San Francisco, California, USA Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA

The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Read More

Neurosurg Focus 2016 Jul;41(1):E10

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio;

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Read More

PLoS One 2016 13;11(4):e0153425. Epub 2016 Apr 13.

Scuola Internazionale Superiore di Studi Avanzati (SISSA), Functional and Structural Genomics sector, Trieste, Italy.

Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Read More

PDA J Pharm Sci Technol 2016 Mar-Apr;70(2):177-88. Epub 2016 Mar 28.

European Medicines Agency, London, UK.

The report provides a summary of the presentations at the Virus & TSE Safety Forum 2015 organized by the Parenteral Drug Association (PDA) and held in Cascais, Portugal, from 9 to 11 June, 2015. As with previous conferences of this series, the PDA Virus & TSE Safety Forum 2015 provided an excellent forum for the exchange of information and opinions between the industry, research organizations, and regulatory bodies. Regulatory updates on virus and TSE safety aspects illustrating current topics of discussion at regulatory agencies in Europe and the United States were provided; the conference covered emerging viruses and new virus detection systems that may be used for the investigation of human pathogenic viruses as well as the virus safety of cell substrates and of raw material of ovine/caprine or human origin. Read More

Swiss Med Wkly 2015 12;145:w14212. Epub 2015 Nov 12.

National CJD Research & Surveillance Unit, Western General Hospital, Edinburgh, UK.

The epidemics of classical bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) related to BSE-infected food are coming to an end. The decline in concern about these diseases may invite complacency and questions whether surveillance for human prion diseases is still necessary. This article reviews the main points of surveillance and why it is still needed: animal sources for human prion infection other than BSE cannot be excluded; the potentially increasing circulation of prions between humans by blood, blood products and medical procedures; the prevalence of vCJD prion carriers in the UK; and the scientific study of prion diseases as paradigm for other neurodegenerative diseases with "prion-like" spread of pathological proteins. Read More

Neurosurg Focus 2015 Nov;39(5):E2

Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%. Several forms of the disease have been described, and the most common is the sporadic type. The most challenging aspect of this disease is its diagnosis-the gold standard for definitive diagnosis is considered to be histopathological confirmation-but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. Read More

Biology (Basel) 2015 Nov 13;4(4):785-813. Epub 2015 Nov 13.

ADAS UK, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, UK.

Prions are an enigma amongst infectious disease agents as they lack a genome yet confer specific pathologies thought to be dictated mainly, if not solely, by the conformation of the disease form of the prion protein (PrP(Sc)). Prion diseases affect humans and animals, the latter including the food-producing ruminant species cattle, sheep, goats and deer. Importantly, it has been shown that the disease agent of bovine spongiform encephalopathy (BSE) is zoonotic, causing variant Creutzfeldt Jakob disease (vCJD) in humans. Read More

Epidemiol Mikrobiol Imunol 2015 Sep;64(3):115-20

Human prion diseases are a group of very rare diseases with a unique pathogenesis and, due to an inauspicious prognosis and unavailability of therapy, with fatal consequences. The etiopathogenetic background is the presence of pathologically misfolded prion protein, highly resistant to denaturation, the aggregation and presence of which in the brain tissue causes irreversible neuronal damage. The most frequent prion disease in humans is Creutzfeldt-Jakob disease (CJD) which occurs in sporadic, hereditary/familial, or acquired/infectious/iatrogenic forms. Read More