Sporadic Creutzfeldt-Jacob Disease Research Articles

Sporadic onset Creutzfeldt-Jacob disease: Interesting MRI observations

We describe a 60-year-old woman with "probable" sporadic Creutzfeldt-Jacob disease (CJD) who manifested with two months history of rapidly progressive dementia and abnormal behavior, speech and gait abnormality, excessive sleepiness and myoclonic jerks. Scalp EEG showed diffuse slowing of background activity to delta range and triphasic sharp wave complexes occurring periodically twice in one-second interval. Magnetic resonance Imaging (MRI) of brain revealed high signal intensity on T2 weighted image (T2WI) and fluid attenuated inversion recovery sequences in the caudate and putamen bilaterally. Diffusion weighted images showed bilateral symmetric hyperintense signals in the caudate and putamen. The role of MRI in the diagnosis of CJD is discussed.

DNA polymorphisms of the prion doppel gene region in four different German cattle breeds and cows tested positive for bovine spongiform encephalopathy

Polymorphisms of the prion protein gene PRNP have been shown to influence the susceptibility/resistance to prion infections in human and sheep. In addition, the T174M polymorphism within the flanking prion doppel gene (PRND) was thought to be involved in susceptibility to sporadic Creutzfeldt-Jacob disease. To study a possible influence of DNA polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy (BSE), previously identified and newly isolated DNA polymorphisms were genotyped in all available German cattle that tested positive for BSE. Genotypes and calculated haplotypes were compared with breeding bulls serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh (Swiss Brown) resulted in the isolation of the previously known polymorphisms R50H and R132Q and two novel synonymous single nucleotide polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype analysis of BSE and control animals revealed a significantly different distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not in the other breeds tested. No association to BSE susceptibility was detectable for polymorphisms R50H and A5063T.

Molecular-Imaging Probe 2-(1-{6-[(2-Fluoroethyl)(Methyl) Amino]-2-Naphthyl}Ethylidene) Malononitrile Labels Prion PlaquesIn Vitro

The study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (FDDNP) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed Gerstmann-Sträussler-Scheinker disease, sporadic Creutzfeldt-Jacob disease (CJD) with kuru plaques, and variant CJD (vCJD). FDDNP is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent substance, whose radiofluorinated analog [18F]FDDNP has recently been successfully used to label senile plaques and neurofibrillary tangles in the living brain of Alzheimer's disease patients with positron emission tomography. Our results show that FDDNP reliably identifies all prion plaques, including small cluster-plaques in vCJD. This finding may open new in vivo diagnostic possibilities for vCJD.

Expression patterns of antioxidant proteins in brains of patients with sporadic Creutzfeldt-Jacob disease.

Using two-dimensional gel electrophoresis (2-DE) and Western blot analysis, we were able to identify and quantify six antioxidant proteins, peroxiredoxin (Prx) I, Prx II, Prx III, 1-Cys Prx, putative peroxisomal antioxidant enzyme (PLP), and mitochondrial Mn superoxide dismutase (Mn-SOD) in two individual brain regions, cerebellum and frontal cortex of patients with sporadic Creutzfeldt-Jacob (sCJD). Among six antioxidant proteins, 1-Cys Prx showed significant increase (P > 0.05) in sCJD frontal cortex whereas Prx I was decreased (P > 0.01). In cerebellum, levels of all antioxidant proteins studied were comparable to those of controls. Our findings provide evidence for the link between aberrant expression of antioxidant proteins, 1-Cys Prx and Prx I and CJD neuropathogenesis and we discuss the neuropathological meaning of these dysregulated antioxidant proteins in sCJD brain.

Prion diseases: epidemiology in man.

Prion disease in man was first described as Creutzfeldt-Jacob disease (CJD) in the 1920s. CJD may have three different origins: sporadic, familial, due to mutations in the prion gene, or infectious, due to iatrogenic exposure to infectious brain material. As an example of the latter, kuru, in Papua New Guinea, was a variant of CJD transmitted by cannibalism. Between 1957 and 1982 more than 2500 died of kuru. Sporadic CJD is the most common form of CJD and occurs with an incidence of around one per million in most parts of the world. Familial CJD accounts for approximately 10% of all European cases of CJD, and is associated with inherited mutations of the prion protein gene, caused by one of the 24 single amino acid substitutions or insertions of octapeptide repeats. CJD caused by infections involves either iatrogenic cases of CJD, resulting from exposure to infectious brain, pituitary or ocular tissue, or from ingestion of infected food items. As of today, a few hundred iatrogenic cases of CJD have been diagnosed worldwide, the majority due to transmission by cadaveric pituitary HCG. So far, 111 cases of vCJD have been diagnosed caused by BSE-contaminated food. The size of the epidemic is still unclear and worst-case scenarios indicate that we may expect many thousands of cases in the future.

Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene

The clinical course, neuropathological features, and genetic findings in 3 members of a German family carrying a novel 120-bp insertion in the prion protein (PrP) gene are described. Genetic analysis of the mutated allele revealed a sequence of five extra octapeptide repeats, distinct from those of the two previously reported families with an insertion of this size. There was distinctive variation in the clinical course and the onset and duration of the illness in the documented subjects. Neuropathological evaluation showed neuronal loss and gliosis in the neocortex of the 3 examined cases; spongiform degeneration was found in 2 of them. PrP immunoreactivity of unusual morphology and distinct distribution was present in the cerebellum and neocortex ("blurred staining") of 2 examined cases. One subject showed features usually found in sporadic Creutzfeldt-Jakob disease with a punctate type of PrP deposition in the cerebellum. In addition, there were some plaque-like PrP aggregates morphologically similar to the other 2 cases in the molecular layer of the cerebellum, and unusual PrP immunoreactivity ("fleecy staining") was found in the neocortex. The clinicopathological heterogeneity in the documented family is in accordance with the phenotypic variability associated with previously reported insertions.

Is codon 129 of prion protein polymorphic in human beings but not in animals?

In human beings, there is a polymorphism at aminoacid position 129 of the prion protein which influences susceptibility to prion infection. In European populations, the usual distribution pattern is about 50% heterozygosity for methionine/valine (Met/Val), 40% homozygosity for methionine (Met/Met), and 10% for valine (Val/Val). Methionine homozygosity predisposes to sporadic Creutzfeldt Jakob disease (CJD) as well as acquired CJD. 1 Palmer MS Dryden AJ Hughes JT et al. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jacob disease. Nature. 1991; 352: 340-342 Crossref PubMed Scopus (737) Google Scholar In patients with new variant CJD (nvCJD) Met/Met has been invariably found. 2 Will RG Ironside JW Zeidler M et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996; 347: 921-925 Summary PubMed Scopus (1877) Google Scholar Structural models ascribe importance to position 129 in stabilising the conformation of PrP by interaction with other aminoacid residues. Conformational change from α-helical to β-sheet structure is thought to be a primary event in prion diseases. The figure shows the location of the α-helical regions revealed by computer-assisted structure prediction and of structural regions determined by a nuclear magnetic resonance-based model of murine PrP (121–231). 3 Riek R Hornemann S Wider G Billeter M Glockshuber R Wüthrich K NMR structure of the mouse protein domain PrP (121–231). Nature. 1996; 382: 180-182 Crossref PubMed Scopus (1114) Google Scholar