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Nat Rev Neurol 2021 May 10. Epub 2021 May 10.

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

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. Read More

PLoS Pathog 2021 Feb 18;17(2):e1009276. Epub 2021 Feb 18.

The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, Edinburgh, United Kingdom.

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. Read More

Viruses 2020 12 17;12(12). Epub 2020 Dec 17.

Centre for Prions and Protein Folding Diseases, Edmonton, AB T6G 2R3, Canada.

The majority of human prion diseases are sporadic, but acquired disease can occur, as seen with variant Creutzfeldt-Jakob disease (vCJD) following consumption of bovine spongiform encephalopathy (BSE). With increasing rates of cervid chronic wasting disease (CWD), there is concern that a new form of human prion disease may arise. Currently, there is no evidence of transmission of CWD to humans, suggesting the presence of a strong species barrier; however, in vitro and in vivo studies on the zoonotic potential of CWD have yielded mixed results. Read More

J Neurol Sci 2021 01 7;420:117221. Epub 2020 Nov 7.

National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. Electronic address:

Creutzfeldt-Jakob disease (CJD) is a fatal human prion disease. Surveillance systems operate globally with the goals of accurate in-life case ascertainment, appropriate public health interventions to minimise secondary transmission, and monitoring trends in disease epidemiology. The UK experienced the highest incidence of variant CJD (vCJD) in the world following widespread population exposure to bovine spongiform encephalopathy (BSE). Read More

JAMA Netw Open 2020 10 1;3(10):e2020690. Epub 2020 Oct 1.

Washington State Department of Health, Shoreline.

Importance: Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans.

Objective: To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. Read More

J Neurol Neurosurg Psychiatry 2020 11 14;91(11):1181-1188. Epub 2020 Sep 14.

IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy

Objective: To compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.

Methods: We used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease. Read More

Biologicals 2020 Sep 6;67:56-61. Epub 2020 Aug 6.

U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Division of Emerging and Transfusion Transmitted Diseases, Silver Spring, MD, 20993, USA. Electronic address:

Heparin is an anticoagulant sourced from animal tissues. In the 1990s, bovine-sourced heparin was withdrawn from the U.S. Read More

Emerg Infect Dis 2020 06;26(6):1130-1139

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet, TgMet/Val, and TgVal. Read More

Emerg Infect Dis 2020 06;26(6):1300-1303

We investigated a clinical case of variant Creutzfeldt-Jakob Disease in a person heterozygous for methionine/valine at codon 129 of the prion protein gene and identified the same strain properties in variant Creutzfeldt-Jakob disease in methionine homozygous persons and in bovine spongiform encephalopathy. These results indicate no adaptation of the agent in a different genetic background. Read More

Parkinsonism Relat Disord 2020 05 4;74:64-66. Epub 2020 May 4.

Department of Neurology, Ajou University School of Medicine, South Korea. Electronic address:

Acta Neuropathol 2020 06 30;139(6):965-976. Epub 2020 Mar 30.

Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology Queen Square, London, WC1N 3BG, United Kingdom.

Widespread dietary exposure of the population of Britain to bovine spongiform encephalopathy (BSE) prions in the 1980s and 1990s led to the emergence of variant Creutzfeldt-Jakob Disease (vCJD) in humans. Two previous appendectomy sample surveys (Appendix-1 and -2) estimated the prevalence of abnormal prion protein (PrP) in the British population exposed to BSE to be 237 per million and 493 per million, respectively. The Appendix-3 survey was recommended to measure the prevalence of abnormal PrP in population groups thought to have been unexposed to BSE. Read More

Pathogens 2020 Mar 14;9(3). Epub 2020 Mar 14.

Center for Neurodegenerative Science, Van Andel Institute, 333 Bostwick Avenue N.E., Grand Rapids, MI 49503, USA.

The term "prion disease" encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant Creutzfeldt-Jakob disease in humans; (b) the heated debate about the prion hypothesis; and (c) the availability of a natural prion disease in rodents, the understanding of the pathogenic process in prion disease is much more advanced compared to that of other neurodegenerative disorders, which inspired many attempts to develop therapeutic strategies against these fatal diseases. Read More

Biomolecules 2020 03 5;10(3). Epub 2020 Mar 5.

Fondazione IRCCS Istituto Neurologico Carlo Besta, Division of Neurology 5-Neuropathology, 20133 Milan, Italy.

Prion diseases are neurodegenerative and invariably fatal conditions that affect humans and animals. In particular, Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE) are paradigmatic forms of human and animal prion diseases, respectively. Human exposure to BSE through contaminated food caused the appearance of the new variant form of CJD (vCJD). Read More

Pharmacoepidemiol Drug Saf 2020 05 5;29(5):575-581. Epub 2020 Mar 5.

FDA Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology, Silver Spring, Maryland.

Purpose: In the late1990s, reacting to the outbreak of bovine spongiform encephalopathy (BSE) in the United Kingdom that caused a new variant of Creutzfeldt-Jakob disease (vCJD) in humans, manufacturers withdrew bovine heparin from the market in the United States. There have been growing concerns about the adequate supply and safety of porcine heparin. Since the BSE epidemic has been declining markedly, the US Food and Drug Administration reevaluates the vCJD risk via use of bovine heparin. Read More

Biomolecules 2020 02 12;10(2). Epub 2020 Feb 12.

Department of Neurology, National Reference Center for CJD Surveillance, University Medical Centre Göttingen, 37075 Göttingen, Germany.

Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt-Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. Read More

Emerg Infect Dis 2020 01;26(1):34-43

Variant Creutzfeldt-Jakob disease (vCJD) is caused by prion infection with bovine spongiform encephalopathy and can be transmitted by blood transfusion. Protein misfolding cyclic amplification (PMCA) can detect prions in blood from vCJD patients with 100% sensitivity and specificity. To determine whether PMCA enables prion detection in blood during the preclinical stage of infection, we performed a blind study using blood samples longitudinally collected from 28 control macaques and 3 macaques peripherally infected with vCJD. Read More

Sci Rep 2019 10 30;9(1):15699. Epub 2019 Oct 30.

Centro de Investigación en Sanidad Animal (INIA-CISA), 28130, Valdeolmos, Madrid, Spain.

Cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-Bovine Spongiform Encephalopathy (classical-BSE) infectious agent. PrP amino acid sequence is considered to play a key role in the susceptibility to prion strains and only one amino acid change may alter this susceptibility. Macaque and human-PrP sequences have only nine amino acid differences, but the effect of these amino acid changes in the susceptibility to dissimilar prion strains is unknown. Read More

BMJ Open 2019 10 28;9(10):e033744. Epub 2019 Oct 28.

Centre for Clinical Brain Sciences, National CJD Research & Surveillance Unit, Edinburgh, UK.

Introduction: Creutzfeldt-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. Read More

Sci Rep 2019 10 24;9(1):15261. Epub 2019 Oct 24.

Korea Zoonosis Research Institute, Chonbuk National University, Iksan, 54531, Republic of Korea.

Prion diseases in sheep and goats are called scrapie and belong to a group of transmissible spongiform encephalopathies (TSEs) caused by the abnormal misfolding of the prion protein encoded by the prion protein gene (PRNP). The shadow of the prion protein gene (SPRN) is the only prion gene family member that shows a protein expression profile similar to that of the PRNP gene in the central nervous system. In addition, genetic susceptibility of the SPRN gene has been reported in variant Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE) and scrapie. Read More

Annu Rev Genet 2019 12 19;53:117-147. Epub 2019 Sep 19.

Medical Research Council Prion Unit at UCL, Institute of Prion Diseases, University College London, London W1W 7FF, United Kingdom; email:

Mammalian prion diseases are a group of neurodegenerative conditions caused by infection of the central nervous system with proteinaceous agents called prions, including sporadic, variant, and iatrogenic Creutzfeldt-Jakob disease; kuru; inherited prion disease; sheep scrapie; bovine spongiform encephalopathy; and chronic wasting disease. Prions are composed of misfolded and multimeric forms of the normal cellular prion protein (PrP). Prion diseases require host expression of the prion protein gene () and a range of other cellular functions to support their propagation and toxicity. Read More

J Hosp Infect 2020 Jan 10;104(1):92-110. Epub 2019 Aug 10.

Erasmus University Medical Center, Department of Medical Microbiology and Infectious Diseases, Rotterdam, The Netherlands; ESCMID Study Group on Nosocomial Infections.

Several guidelines recommend specific treatments for endoscopes, procedures of quarantine for endoscopes, or additional treatments for the endoscope washer disinfector (EWD) in suspected or confirmed cases of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD) but vary in many details. This study therefore reviewed guidelines on reprocessing flexible endoscopes after use in patients with suspected or confirmed prion disease. In addition, a literature search was performed in Medline on prion, CJD, vCJD, chemical inactivation, transmission healthcare, epidemiology healthcare, concentration tissue human and endoscope. Read More

Lab Invest 2019 11 27;99(11):1741-1748. Epub 2019 Jun 27.

Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Prion diseases are transmissible neurological disorders associated with the presence of abnormal, disease-related prion protein (PrP). The detection of PrP in the brain is the only definitive diagnostic evidence of prion disease and its identification in body fluids and peripheral tissues are valuable for pre-mortem diagnosis. Protein misfolding cyclic amplification (PMCA) is a technique able to detect minute amount of PrP and is based on the conversion of normal or cellular PrP (PrP) to newly formed PrP, sustained by a self-templating mechanism. Read More

J Alzheimers Dis Parkinsonism 2019 29;8(6). Epub 2018 Nov 29.

Department of Physiology, Medical Sciences Building, University of Toronto, Toronto ON M5S 1A8, CANADA.

Aluminum is a ubiquitous neurotoxin highly enriched in our biosphere, and has been implicated in the etiology and pathology of multiple neurological diseases that involve inflammatory neural degeneration, behavioral impairment and cognitive decline. Over the last 36 years our group has analyzed the aluminum content of the temporal lobe neocortex of 511 high quality coded human brain samples from 18 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Brodmann anatomical areas including the inferior, medial and superior temporal gyrus (A20-A22) were selected for analysis: (i) because of their essential functions in massive neural information processing operations including cognition and memory formation; and (ii) because subareas of these anatomical regions are unique to humans and are amongst the earliest areas affected by progressive neurodegenerative disorders such as Alzheimer's disease (AD). Read More

PLoS One 2019 16;14(5):e0216807. Epub 2019 May 16.

Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki, Japan.

Classical- (C-) and atypical L-type bovine spongiform encephalopathy (BSE) prions cause different pathological phenotypes in cattle brains, and the disease-associated forms of each prion protein (PrPSc) has a dissimilar biochemical signature. Bovine C-BSE prions are the causative agent of variant Creutzfeldt-Jakob disease. To date, human infection with L-BSE prions has not been reported, but they can be transmitted experimentally from cows to cynomolgus monkeys (Macaca fascicularis), a non-human primate model. Read More

Neurology 2019 04 6;92(14):675-677. Epub 2019 Mar 6.

From Johns Hopkins School of Medicine (T.H., C.M., L.S., J.C.P.), Baltimore, MD; Case Western Reserve University School of Medicine (M.C., J.S.), Cleveland, OH; and National Center for Emerging and Zoonotic Infectious Diseases (L.B.S.), Centers for Disease Control and Prevention, Atlanta, GA.

Cent Eur J Public Health 2018 Dec;26 Suppl:S37-S41

Department of Neurology, Faculty of Medicine, Pavol Jozef Safarik University in Kosice and Louis Pasteur University Hospital, Kosice, Slovak Republic.

Objectives: An extraordinary incidence of genetic Creutzfeldt-Jakob disease (gCJD) appearing in clusters in the Slovak Republic was described in the 1990's. The aim of the study was to analyse data of CJD cases obtained from surveillance in Eastern Slovakia (ES) (2004-2016), the region outside the described geographical clusters.

Methods: The database set in the project was the source for epidemiological and clinical analysis of CJD cases. Read More

Mol Neurobiol 2019 Feb 31;56(2):1531-1538. 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 2019 03 22;29(2):248-262. Epub 2019 Jan 22.

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

J Neurol Neurosurg Psychiatry 2019 04 24;90(4):424-427. Epub 2018 Oct 24.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

Objective: To assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD).

Methods: We examined medical records of 117 sCJDVV2 (ataxic type), 65 sCJDMV2K (kuru-plaque type) and 121 sCJDMM(V)1 (myoclonic type) subjects for clinical symptoms, objective signs and neurophysiological data. We reviewed two diagnostic nerve biopsies and looked for abnormal prion protein (PrP) by western blotting and real-time quaking-induced conversion (RT-QuIC) in postmortem PNS samples from 14 subjects. Read More