Development of an Automated Capillary Immunoassay to Detect Prion Glycotypes in Creutzfeldt-Jakob Disease.

Creutzfeldt-Jakob disease (CJD) comprises a group of transmissible neurodegenerative diseases with vast phenotypic diversity. Sporadic CJD heterogeneity is predominantly influenced by the genotype at codon 129 of the prion-encoding gene and the molecular weight of PrP fragments after protease digestion, resulting in a classification of 6 subtypes of CJD (MM1, MM2, MV1, MV2, VV1, and VV2). The majority of cases with CJD can be distinguished using this classification system.

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.

Identification of circulating microRNA signatures as potential biomarkers in the serum of elk infected with chronic wasting disease.

Chronic wasting disease (CWD) is an emerging infectious prion disorder that is spreading rapidly in wild populations of cervids in North America. The risk of zoonotic transmission of CWD is as yet unclear but a high priority must be to minimize further spread of the disease. No simple diagnostic tests are available to detect CWD quickly or in live animals; therefore, easily accessible biomarkers may be useful in identifying infected animals.

Sporadic Creutzfeldt-Jakob Disease in a Young Girl With Unusually Long Survival.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal degenerative encephalopathy caused by a pathologically altered form of the prion protein (PrP). CJD is rare, with 1 and 2 cases per million per year reported in the general population, mostly in individuals over 50 years of age. It is almost unknown in the pediatric population.

A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles.

To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.

A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia.

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.

Creutzfeldt-Jakob disease mortality in Canada, 1998 to 2013.

Background: Human prion diseases, known collectively as Creutzfeldt-Jakob disease (CJD), are fatal, infectious neurodegenerative disorders that occur in all human populations.

Objective: To summarize national surveillance data for CJD in Canada between January 1, 1998, and December 31, 2013.

Methods: Detailed investigations were conducted of individual suspected CJD cases, with collaboration between Canadian health professionals and investigators affiliated with a central CJD surveillance registry operated by the Public Health Agency of Canada.

Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using cerebrospinal fluid.

Unlabelled: Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days.

Is there a risk of chikungunya transmission in Canada?

An outbreak of chikungunya virus infection is currently underway in the Caribbean, Central America and South America, and autochthonous (local or indigenous) transmission has occurred in the southeastern United States. The mosquito species known to transmit chikungunya- and -are not known to reside in Canada at this time. But how comfortable can we be that this situation will continue? Here we explore four key conditions that must be met for transmission of chikungunya within Canada.

West Nile virus in Canada: ever-changing, but here to stay.

The incidence of West Nile virus (WNv) has waxed and waned in Canada over the past 12 years, but it is unlikely to disappear. Climate change models, which suggest warming temperatures and changing patterns of precipitation, predict an expansion of geographic range for WNv in some regions of Canada, such as the Prairie provinces. Such projected changes in WNv distribution might also be accompanied by genetic changes in the virus and/or the range of bird and insect host species it infects.

Evidence for synergistic effects of PRNP and ATP7B mutations in severe neuropsychiatric deterioration.

Background: Wilson's disease (WD), a rare cause of neuropsychiatric deterioration, is associated with mutations in the ATP7B gene. Prion diseases are also rare causes of neuropsychiatric deterioration that can occur sporadically without an identifiable cause, or can be attributed to mutations in the PRNP gene.

Case Presentation: Here we describe a biological "experiment of nature" in which a patient presented with severe neuropsychiatric decline and strong biochemical evidence of WD.

Exploring physical and chemical factors influencing the properties of recombinant prion protein and the real-time quaking-induced conversion (RT-QuIC) assay.

Real-time quaking-induced conversion (RT-QuIC), a highly specific and sensitive assay able to detect low levels of the disease-inducing isoform of the prion protein (PrP(d)) in brain tissue biopsies and cerebral spinal fluid, has great potential to become a method for diagnosing prion disease ante mortem. In order to standardize the assay method for routine analysis, an understanding of how physical and chemical factors affect the stability of the recombinant prion protein (rPrP) substrate and the RT-QuIC assay's sensitivity, specificity, and reproducibility is required. In this study, using sporadic Creutzfeldt-Jakob Disease brain homogenate to seed the reactions and an in vitro-expressed recombinant prion protein, hamster rPrP, as the substrate, the following factors affecting the RT-QuIC assay were examined: salt and substrate concentrations, substrate storage, and pH.

The prion protein modulates A-type K+ currents mediated by Kv4.2 complexes through dipeptidyl aminopeptidase-like protein 6.

Widely expressed in the adult central nervous system, the cellular prion protein (PrP(C)) is implicated in a variety of processes, including neuronal excitability. Dipeptidyl aminopeptidase-like protein 6 (DPP6) was first identified as a PrP(C) interactor using in vivo formaldehyde cross-linking of wild type (WT) mouse brain. This finding was confirmed in three cell lines and, because DPP6 directs the functional assembly of K(+) channels, we assessed the impact of WT and mutant PrP(C) upon Kv4.

Insights into origins of Human T-cell Lymphotropic Virus Type 1 based on new strains from aboriginal people of Canada.

The causes of the worldwide distribution of Human T-cell Lymphotropic Virus Type 1 (HTLV-1) remain incompletely understood, with competing hypotheses regarding the number and timing of events leading to intercontinental spread on historical and prehistoric timescales. Ongoing discovery of this virus in aboriginal populations of Asia and the Americas has been the main source of evidence for the latter. We conducted molecular phylogenetic and dating analyses for 13 newly reported HTLV-1 strains from Canada.

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study.

Background: To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD.

Methods: The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses.

Using qualitative methods to investigate risk perception of Canadian medical laboratory workers in relation to current prion disease infection control policies.

The aim of this study was to determine the rationale, methodology, and progress of risk perceptions of laboratory workers in relation to existing prion disease infection control policies in Canadian medical laboratories. This study developed a Web survey that investigated the knowledge, behavior, and attitudes of laboratory staff in order to (1) identify strengths, weaknesses, and gaps of current prion infection prevention and control guidelines and (2) inform the development of national medical lab specific guidelines. The use of qualitative methods to develop a relevant survey is described and future research activities are outlined.

Molecular, biochemical and genetic characteristics of BSE in Canada.

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrP(res)). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrP(res), including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity.

MRI lesion profiles in sporadic Creutzfeldt-Jakob disease.

Background: With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. This multicenter, international study aimed to describe the brain MRI findings associated with each of the sCJD molecular subtypes.

Species barriers for chronic wasting disease by in vitro conversion of prion protein.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that can affect North American cervids (deer, elk, and moose). Using a novel in vitro conversion system based on incubation of prions with normal brain homogenates, we now report that PrP(CWD) of elk can readily induce the conversion of normal cervid PrP (PrP(C)) molecules to a protease-resistant form, but is less efficient in converting the PrP(C) of other species, such as human, bovine, hamster, and mouse. However, when substrate brain homogenates are partially denatured by acidic conditions (pH 3.

Human transmissible spongiform encephalopathies in eleven countries: diagnostic pattern across time, 1993-2002.

Background: The objective of this study was to describe the diagnostic panorama of human transmissible spongiform encephalopathies across 11 countries.

Methods: From data collected for surveillance purposes, we describe annual proportions of deaths due to different human transmissible spongiform encephalopathies in eleven EUROCJD-consortium countries over the period 1993-2002, as well as variations in the use of diagnostic tests. Using logistic models we quantified international differences and changes across time.