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Vox Sang 2022 May 24. Epub 2022 May 24.

Australian Red Cross Lifeblood, Melbourne, Victoria, Australia.

Background And Objectives: Most of the 233 worldwide cases of variant Creutzfeldt-Jakob disease (vCJD) have been reported in the United Kingdom and 3 have been associated with transfusion-transmission. To mitigate the potential vCJD risk to blood safety, Australian Red Cross Lifeblood imposes restrictions on blood donation from people with prior residency in, or extended travel to, the United Kingdom during the risk period 1980-1996. We have modified a previously published methodology to estimate the transfusion-transmission risk of vCJD associated with fresh component transfusion in Australia if the UK residence deferral was removed. Read More

BMJ Neurol Open 2022 18;4(1):e000299. Epub 2022 Apr 18.

Department of Neurosciences, Alfred Hospital, Melbourne, Victoria, Australia.

Background: A diagnosis of variant Creutzfeldt-Jakob disease (vCJD), the zoonotic prion disease related to transmission of bovine spongiform encephalopathy, can carry enormous public health ramifications. Until recently, all vCJD clinical cases were confined to patients displaying methionine homozygosity (MM) at codon 129 of the prion protein gene (). The recent diagnosis of vCJD in a patient heterozygous (MV) at codon 129 reignited concerns regarding a second wave of vCJD cases, with the possibility of phenotypic divergence from MM vCJD and greater overlap with sporadic CJD (sCJD) molecular subtypes. Read More

Cureus 2022 Feb 22;14(2):e22507. Epub 2022 Feb 22.

Internal Medicine, Aurora Medical Center-Bay Area, Marinette, USA.

Creutzfeldt-Jakob disease (CJD) is a very rare neurodegenerative disorder that usually presents as rapidly progressive dementia with an extremely poor prognosis. The diagnosis of CJD can be extremely challenging due to its rarity, manifestation with non-specific neurological symptoms, associated broad differentials, and a need for extensive workup. Awareness of disease-specific biomarkers, radiological signs, and diagnostic criteria are crucial for timely diagnosis. Read More

Folia Neuropathol 2022 ;60(1):24-34

LSU Neuroscience Center, and Departments of Neurology and Ophthalmology, LSU Health Sciences Center, New Orleans, USA.

The pro-inflammatory, innate-immune system ribonucleic acid mediator microRNA-146a, constitutively expressed in the brain and central nervous system (CNS) of both the mouse and the human, is pathologically up-regulated in multiple transmissible spongiform encephalopathies (TSEs) to several times its basal level. miRNA-146a: (i) exists as a ~22-ribonucleotide (nt) single-stranded non-coding RNA (sncRNA) whose sequence is unique and highly selected over evolution; (ii) is brain-, CNS- and lymphoid-tissue enriched and exhibits a 100% RNA sequence homology between the mouse and the human; (iii) has been repeatedly shown to play critical immunological and pro-inflammatory roles in the onset and propagation of several human CNS disorders including progressive, incapacitating, and lethal neurological syndromes that include prion disease (PrD) and Alzheimer's disease (AD); (iv) is a fascinating molecular entity because it is representative of the smallest class of soluble, information-carrying, amphipathic sncRNA yet described; (v) has capability to be induced by cellular stressors and the pro-inflammatory transcription factor NF-kB (p50/p65); (vi) has capability to post-transcriptionally regulate multiple mRNAs and cellular processes in neurological health and disease; (vii) is upregulated in human host cells after viral invasion by single-stranded RNA (ssRNA) or double-stranded DNA (dsDNA) neurotropic viruses; and (viii) has an immense potential in neuro-degenerative disease therapeutics via anti-NF-kB and/or anti-miRNA-146a treatment strategies. In this short communication we provide for the first time evidence that miRNA-146a is a prominent sncRNA species in experimental murine prion disease, progressively increasing in the pre-symptomatic stages in C57BL/6J, SJL/J or Swiss Albino murine scrapie prion models. Read More

Lancet Neurol 2022 04;21(4):342-354

MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK; National Prion Clinic, National Hospital for Neurology and Neurosurgery, London, UK. Electronic address:

Background: Human prion diseases, including Creutzfeldt-Jakob disease (CJD), are rapidly progressive, invariably fatal neurodegenerative conditions with no effective therapies. Their pathogenesis involves the obligate recruitment of cellular prion protein (PrP) into self-propagating multimeric assemblies or prions. Preclinical studies have firmly validated the targeting of PrP as a therapeutic strategy. Read More

Neurobiol Dis 2022 03 10;164:105625. Epub 2022 Jan 10.

Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany; Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum Jülich, Jülich, Germany. Electronic address:

In several neurodegenerative disorders, proteins that typically exhibit an α-helical structure misfold into an amyloid conformation rich in β-sheet content. Through a self-templating mechanism, these amyloids are able to induce additional protein misfolding, facilitating their propagation throughout the central nervous system. This disease mechanism was originally identified for the prion protein (PrP), which misfolds into PrP in a number of disorders, including variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE). Read More

Pathogens 2021 Oct 30;10(11). Epub 2021 Oct 30.

National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

Twenty-five years has now passed since variant Creutzfeldt-Jakob disease (vCJD) was first described in the United Kingdom (UK). Early epidemiological, neuropathological and biochemical investigations suggested that vCJD represented a new zoonotic form of human prion disease resulting from dietary exposure to the bovine spongiform encephalopathy (BSE) agent. This hypothesis has since been confirmed though a large body of experimental evidence, predominantly using animal models of the disease. Read More

Viruses 2021 09 9;13(9). Epub 2021 Sep 9.

Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON M5T 0S8, Canada.

In sporadic Creutzfeldt-Jakob disease, molecular subtypes are neuropathologically well identified by the lesioning profile and the immunohistochemical PrP deposition pattern in the grey matter (histotypes). While astrocytic PrP pathology has been reported in variant CJD and some less frequent histotypes (e.g. Read More

Int J Mol Sci 2021 Aug 25;22(17). Epub 2021 Aug 25.

LSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.

The human brain and central nervous system (CNS) harbor a select sub-group of potentially pathogenic microRNAs (miRNAs), including a well-characterized NF-kB-sensitive microRNA hsa-miRNA-146a-5p (miRNA-146a). miRNA-146a is significantly over-expressed in progressive and often lethal viral- and prion-mediated and related neurological syndromes associated with progressive inflammatory neurodegeneration. These include ~18 different viral-induced encephalopathies for which data are available, at least ~10 known prion diseases (PrD) of animals and humans, Alzheimer's disease (AD) and other sporadic and progressive age-related neurological disorders. Read More

J Am Med Dir Assoc 2022 May 4;23(5):845-851. Epub 2021 Sep 4.

Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Psychology, College of Science, National Taiwan University, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan. Electronic address:

Objectives: To study the prognostic features of Creutzfeldt-Jakob disease (CJD) and shed light on its future therapy.

Design: Retrospective cohort study of a longitudinal national cohort of the Taiwan Centers for Disease Control.

Setting And Participants: All patients with suspected CJD are reported to the CJD surveillance unit of the Taiwan Centers for Disease Control. Read More

Acta Neuropathol Commun 2021 08 28;9(1):145. Epub 2021 Aug 28.

UMR INRAE ENVT 1225, Interactions Hôtes-Agents Pathogènes, École Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076, Toulouse, France.

Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different. Read More

Prion 2021 12;15(1):94-106

Department of Neurodegeneration, Ageing and Mental Health, National Epidemiology Centre, Carlos III Health Institute, Madrid, Spain.

In Spain, human transmissible spongiform encephalopathies (TSEs) have been undergoing continuous surveillance for over 25 years. In 1995, the system was launched as an EU Concerted Action, with EU surveillance network procedures being incorporated from 2002 onwards. The aim of this report was to describe performance and outcomes of this surveillance system across the period 1993-2018. Read More

Eur Radiol 2021 Dec 12;31(12):9073-9085. Epub 2021 May 12.

Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Objective: To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD).

Methods: A systematic literature search of the MEDLINE and EMBASE databases was performed, since their inception up to July 28, 2020. Pooled diagnostic yield of diffusion-weighted imaging was calculated using DerSimonian-Laird random-effects model. Read More

Nat Rev Neurol 2021 06 10;17(6):362-379. 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

J Alzheimers Dis 2021 ;81(2):769-785

National Dementia BioBank. Ciencias Biológicas, Facultad de Estudios Superiores, Cuautitlán, UNAM, Estado de México, México.

Background: Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called "prion", which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. Read More

PLoS Pathog 2021 02 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

Acta Neurol Belg 2021 Apr 24;121(2):341-349. Epub 2021 Jan 24.

Department of Neuroscience, Leeds Teaching Hospitals, NHS Trust, Leeds, UK.

Creutzfeld-Jakob disease (CJD) is a fatal neurodegenerative disease which belongs to the family of transmissible spongiform encephalopathies (TSEs), or prion diseases. Historically, CJD diagnosis has been based on the combination of clinical features and in vivo markers, including CSF protein assays, MRI and EEG changes. Brain-derived CSF proteins, such as 14-3-3, t-tau and p-tau have been largely used to support the diagnosis of probable CJD, although with certain limitations concerning sensitivity and specificity of these tests. 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