Subject(s)
Brain/pathology , Codon/genetics , Creutzfeldt-Jakob Syndrome/diagnosis , Creutzfeldt-Jakob Syndrome/genetics , Prions/genetics , Threonine/genetics , tau Proteins/genetics , 14-3-3 Proteins/genetics , Adult , Amino Acid Substitution/genetics , Blotting, Western , Dementia/diagnosis , Dementia/genetics , Dementia/pathology , Enzyme-Linked Immunosorbent Assay , Gene Expression/genetics , Genetic Carrier Screening , Humans , Magnetic Resonance Imaging , Male , Methionine/genetics , Nerve Growth Factors/genetics , Phosphorylation/genetics , Prion Proteins , Pulvinar/pathology , S100 Calcium Binding Protein beta Subunit , S100 Proteins/genetics , Valine/geneticsSubject(s)
Blood Donors , Blood Transfusion , Brain/pathology , Creutzfeldt-Jakob Syndrome/pathology , Creutzfeldt-Jakob Syndrome/transmission , Blotting, Western , Brain/metabolism , Cerebellum/metabolism , Cerebellum/pathology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Creutzfeldt-Jakob Syndrome/metabolism , Humans , Immunohistochemistry , Middle Aged , Prions/metabolism , Young AdultABSTRACT
TSEs (transmissible spongiform encephalopathies) are neurodegenerative diseases of various mammalian species, the best known of which include BSE (bovine spongiform encephalopathies) in cattle, CJD (Creutzfeldt-Jakob disease) in humans, scrapie in sheep and CWD (chronic wasting disease) in deer. This review examines the emergence of various TSE strains and their transmission, and discusses disease surveillance and control.
Subject(s)
Creutzfeldt-Jakob Syndrome/genetics , Genetic Variation , Prion Diseases/epidemiology , Prion Diseases/transmission , Creutzfeldt-Jakob Syndrome/classification , Creutzfeldt-Jakob Syndrome/epidemiology , Humans , Incidence , Prion Diseases/classification , Prion Diseases/prevention & controlABSTRACT
BACKGROUND: Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility. METHODS: Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene. Since the human PrP gene has variation at codon 129, with MM, VV, and MV genotypes, three inbred lines with an identical genetic background were produced to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were inoculated with BSE or vCJD and assessed for clinical and pathological signs of disease. FINDINGS: BSE was transmitted to the bovine line but did not transmit to the human lines. By contrast, vCJD was transmitted to all three human lines with different pathological characteristics for each genotype and a gradation of transmission efficiency from MM to MV to VV. INTERPRETATION: Transmission of BSE to human beings is probably restricted by the presence of a significant species barrier. However, there seems to be a substantially reduced barrier for human-to-human transmission of vCJD. Moreover, all individuals, irrespective of codon-129 genotype, could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue.
Subject(s)
Amyloid/genetics , Creutzfeldt-Jakob Syndrome/transmission , Encephalopathy, Bovine Spongiform/transmission , Genetic Predisposition to Disease , Protein Precursors/genetics , Animals , Blood Transfusion , Cattle , Codon , Humans , Iatrogenic Disease , Mice , Mice, Transgenic , Polymorphism, Genetic , Prion Proteins , Prions , Risk Factors , ZoonosesABSTRACT
The authors performed analysis of the prion protein gene (PRNP) in 27 out of 109 confirmed prion disease patients between 1994 and 2004. E200K mutation was found in 17 cases. Another 10 patients, lacking PRNP analysis, showed positive family history. The mean annual incidence (0.27/million) and proportion (25.6%) of genetic prion disease is unusually high in Hungary and might be related to the migration of ancestors from the Slovakian focus.
