Disease relevance of Creutzfeldt-Jakob Syndrome

• Prion diseases are transmissible neurodegenerative conditions that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) and scrapie in animals [1].
• Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy, new variant Creutzfeldt-Jakob disease, kuru and most cases of iatrogenic Creutzfeldt-Jakob disease [2].
• We investigated the allelic origin of PrP(res) in brains of subjects heterozygous for the D178N mutation linked to fatal familial insomnia (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD178), as well as for insertional mutations associated with another CJD subtype [3].
• The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease [4].
• Similar results were observed in humans affected with sporadic and variant Creutzfeldt-Jakob disease, implicating for the first time the caspase-12 dependent pathway in a neurodegenerative disease in vivo, and thus offering novel potential targets for the treatment of prion disorders [5].

Psychiatry related information on Creutzfeldt-Jakob Syndrome

• These data suggest including detection of p130/131 as a criterion for the diagnosis of probable CJD in addition to the currently accepted criteria of a rapidly progressive dementia of less than 2 years duration, typical neurological signs, and periodic sharp-wave complexes in the EEG [6].
• At various times, family members have carried diagnoses of Alzheimer's disease, Huntington's disease, Parkinson's disease, myoclonic epilepsy, atypical dementia, Pick's disease, Creutzfeldt-Jakob disease and Gerstmann-Sträussler syndrome [7].
• Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from Alzheimer's disease (AD) and Down's syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD) [8].
• A patient given bismuth nitrate in the recommended dose range over 16 months developed panic attacks and a major depressive syndrome and, after 15 months, a myoclonic encephalopathy resembling Creutzfeldt-Jakob disease [9].
• Here we present IVL in a 78-year-old woman with findings leading to the clinical diagnosis of vascular dementia with sudden beginning and positive 14-3-3 protein in the CSF, commonly reported in Creutzfeldt-Jakob disease (CJD) [10].

High impact information on Creutzfeldt-Jakob Syndrome

• The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt-Jakob disease [11].
• Routine use of phenolized formalin in fixation of autopsy brain tissue to reduce risk of inadvertent transmission of Creutzfeldt-Jakob disease [12].
• Creutzfeldt-Jakob disease is caused by a slow infectious pathogen, or prion [13].
• Our findings suggest that the amyloid plaques found in the brains of patients with Creutzfeldt-Jakob disease may be composed of paracrystalline arrays of prions similar to those in prion diseases in laboratory animals [13].
• After being stained with Congo red dye, the protein polymers from patients with Creutzfeldt-Jakob disease exhibited green birefringence when examined under polarized light [13].

Chemical compound and disease context of Creutzfeldt-Jakob Syndrome

• Transmission of Creutzfeldt-Jakob disease from formalin-fixed, paraffin-embedded human brain tissue [14].
• Mutations of this protein are linked to familial variants of the disease, and the presence of a methionine or valine residue at the polymorphic position 129 may be critical in sporadic CJD cases [15].
• Acyclovir in Creutzfeldt-Jakob disease [16].
• Repeated suppression of Creutzfeldt-Jakob disease with vidarabine [17].
• Dapsone to delay symptoms in Creutzfeldt-Jakob disease [18].

Biological context of Creutzfeldt-Jakob Syndrome

• Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease [19].
• These data imply that homozygosity for Q-171 codons is necessary but not sufficient for the development of natural scrapie, echo reports of recessive manifestation, and parallel over-representation of PRNP codon 129 homozygotes in Creutzfeldt-Jakob disease of humans [20].
• Although variant CJD can be diagnosed during life by tonsil biopsy, a prion-specific blood test is needed to assess and manage this potential threat to public health [21].
• The apolipoprotein E alleles as major susceptibility factors for Creutzfeldt-Jakob disease. The French Research Group on Epidemiology of Human Spongiform Encephalopathies [22].
• The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide [23].

Anatomical context of Creutzfeldt-Jakob Syndrome

• At a cut-off of 35 ng/mL an optimum sensitivity of 80% with a specificity of 92% for the diagnosis of Creutzfeldt-Jakob disease by NSE in cerebrospinal fluid was obtained [24].
• Progressively increased expression of TNF-alpha in CJD virus-infected brain tissues was verified by Northern and Western blot analyses, and astrocytes in areas with striking myelin sheath vacuolation were intensely stained with an antibody against murine TNF-alpha [25].
• Because quinacrine and chlorpromazine have been used in humans for many years as antimalarial and antipsychotic drugs, respectively, and are known to pass the blood-brain barrier, we suggest that they are immediate candidates for the treatment of Creutzfeldt-Jakob disease and other prion diseases [26].
• The collective findings of TNF-alpha overexpression during the course of clinical disease suggest that TNF-alpha may mediate the myelin sheath vacuolation observed in experimental CJD [25].
• Variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to prions, and exhibit early prion accumulation in germinal centers [27].

Gene context of Creutzfeldt-Jakob Syndrome

• Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease [23].
• Histoblots were also useful in localizing PrPCJD and beta/A4-amyloid peptide in the brains of patients with Creutzfeldt-Jakob disease and Alzheimer disease, respectively [28].
• Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice [25].
• In CJD inoculated mice, loss of PV+ neurons was severe and occurred very early after inoculation [29].
• CONCLUSION: Our results do not support the contention that the APOE epsilon4 allele is a risk factor for developing Creutzfeldt-Jakob disease or related disorders [30].

Analytical, diagnostic and therapeutic context of Creutzfeldt-Jakob Syndrome

• Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses [24].
• Two Creutzfeldt-Jakob disease agents reproduce prion protein-independent identities in cell cultures [31].
• Immunoblotting of Creutzfeldt-Jakob disease prion proteins: host species-specific epitopes [32].
• We studied a 62-year-old man with Creutzfeldt-Jakob disease (CJD), using positron emission tomography (PET) and (18F)-2-fluoro-2-deoxy-D-glucose (FDG) [33].
• BACKGROUND: The 14-3-3 protein immunoassay on CSF has favorable test characteristics as a premortem diagnostic tool in CJD [34].

References