Search

The cause of hyperintense magnetic resonance changes and reduced apparent diffusion coefficient (ADC) in specific brain regions of patients with Creutzfeldt-Jakob disease (CJD) is unknown. Our aim was to determine the neuropathologic correlates of antemortem water ADC and normalized T2-weighted changes in patients with CJD.

The increase of the 14-3-3 protein in CSF is used as a diagnostic test in Creutzfeldt–Jakob disease (CJD), but the sensitivity and specificity of the 14-3-3 test are disputed. One reason for the dispute may be the recently established heterogeneity of sporadic CJD. The relationship between CSF 14-3-3 protein and sporadic CJD subtypes, distinguished by electrophoretic mobility of proteinase K-resistant prion protein (PrPSc) and genotype at codon 129 of the prion protein gene, has not been elucidated.

Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt–Jakob disease (CJD) but is a hallmark of fatal familial insomnia.

To describe the clinical and neuropathologic profile and determine the strain characteristics of familial Creutzfeldt–Jakob disease (fCJD) caused by a point mutation of the PRNPgene at codon 210 that results in a valine-to-isoleucine substitution in the prion protein (PrP).

Iatrogenic Creutzfeldt–Jakob disease (CJD) transmission via dura mater grafts has been reported in many countries. In September 1998, a 39-year-old Colorado woman was reported as having suspected CJD after receiving a dura mater graft 6 years earlier.

To establish a variant of sporadic prion disease as the sporadic form of fatal familial insomnia (FFI).

The conversion of soluble prion protein into an insoluble, pathogenic, protease-resistant isoform is a key event in the development of prion diseases. Although the mechanism by which the conversion engenders a pathogenic event is unclear, there is increasing evidence to suggest that this may depend on the function of the prion protein in preventing oxidative damage. Therefore, in this study, we assessed the interrelationship between redox-sensitive cysteine, glycosylation, and prion metabolism. Cells were treated with a thioreductant, dithiothreitol, to assess the effect of the cellular oxidation state on the synthesis of the prion protein. This change in redox balance affected the glycosylation of the prion protein, resulting in the sole production of glycosylated forms. The role of the single disulfide bridge in mediating this effect within the prion protein was confirmed by mutating the cysteine residues involved in its formation. These data suggest that conditions that increase the rate of formation of the disulfide bridge favor formation of the unglycosylated prion protein. Thus, since the presence of glycans on the prion protein is protective against its pathogenic conversion, a change in the redox status of the cell would increase the risk of developing a prion disease by favoring the production of the unglycosylated form.

A 49-year-old woman presented with isolated aphasia followed by dementia and ataxia with a duration of 4 years. Histopathologically there was panencephalic involvement, status spongiosus, and kuru-type plaques. Molecular analysis showed heterozygosity at codon 129 in the prion protein(PrP) gene, and type 2 protease-resistant PrP. The comparison between this case and those previously reported suggests that the panencephalopathic variant of Creutzfeldt-Jakob disease (CJD) is an aspecific end-stage condition displayed by most if not all CJD variants in individual patients with an unusually prolonged course.

Three members of a Basque family carrying a novel six R2octapeptide repeat 144-bp insertion in the prion protein gene (PRNP) showed a slowly progressive dementia associated with cerebellar signs, myoclonic jerks, and seizures. Although postmortem examination revealed only focal and minimal spongiform degeneration in one subject with a 4-year course, significant astrogliosis and neuronal loss were associated with pronounced spongiform degeneration in the patient with a duration of symptoms of 10 years. Prion protein (PrP)-immunoreactive patches with a unique morphology were present in the molecular layer of the cerebellum in both subjects. Western blot analysis demonstrated the presence of protease-resistant prion protein (PrPres) with the same characteristics (size and ratio of the three differently glycosylated isoforms) of that found in typical sporadic Creutzfeldt-Jakob disease (CJD129M/M, PrPrestype 1). The amount of PrPrescorrelated with presence and severity of spongiform degeneration in the cerebral cortex. The findings suggest that a relatively low rate of PrPresdeposition is the cause of the lack of spongiform degeneration in subjects carrying a 144-bp insertion in PRNP. The presence of PrP-immunoreactive patches with unique morphology in the molecular layer of the cerebellum is a hallmark of certain prion encephalopathies with insertional mutations and is useful in the diagnosis of this subtype of human prion disease.

The authors investigated a patient who died of apparent sporadic Creutzfeldt-Jakob disease (CJD) but carried a R208H substitution in the prion protein (PrP). The patient phenotype was indistinguishable from typical sporadic CJD (i.e., MM1 subtype). In addition, pathologic PrP, PrPSc, originated from both the normal and the mutated PRNPallele and had the same characteristics as PrPSctype 1. The authors propose that the R208H mutation influences disease susceptibility without significantly affecting PrPScproperties or disease phenotype.

A two-octapeptide repeat deletion of the prion protein gene has been recently observed in a patient with a 2-year history of dementia and a clinical diagnosis of possible Creutzfeldt–Jakob disease (CJD). The authors report a similar deletion in a patient with a definitive diagnosis of CJD. Since the two-repeat deletion has not been observed in large, population-based studies, the two cases suggest that this deletion is a new pathogenic mutation associated with CJD.

We examined brain biopsy tissue from five patients with a neurologic syndrome consistent with Creutzfeldt-Jakob disease using Western blot analysis and immunohistochemistry for the detection of protease-resistant prion protein, in addition to histopathologic examination. Our results indicate that the formation of protease-resistant prion protein is an early event in disease pathogenesis and Western blot analysis can detect protease-resistant prion protein in the absence of structural lesions using a small amount of brain biopsy tissue.