Background And Purpose: The aim of the study was to perform molecular analysis in a group of patients affected with prion disease. Diagnosis was based on results of clinical and/or histopathological examination of the brain. This is the largest investigation of this type performed so far in Poland.
Material And Methods: Analysed material contained 36 cases of prion disease, including 35 cases of Creutzfeldt-Jakob disease and one case of Gerstmann-Sträussler-Scheinker disease, as well as two familial cases initially suspected of Huntington disease and Alzheimer disease. The control group consisted of 87 subjects. The most frequent known mutations in the PRNP gene were looked for, namely those in codons 102, 117, 178, 200, 217 and OPRI; the polymorphism Met/Val in codon 129 was also analysed. The methods applied were PCR-RFLP and DNA sequencing.
Results: The following mutations were found: E200K in 5 families, P102L in one family (previously identified), D178N in one family and 6OPRI in one family. Overall, mutations were detected in 17 persons (including 8 preclinical ones) from 8 pedigrees. Highly significant difference of codon 129 Met/Val heterozygosity frequencies was found between the affected subjects and the controls. Frequency of the familial form of prion disease in the material analysed was 14%.
Conclusions: Screening for mutations in the PRNP gene should be performed in all diagnosed cases of prion disease and in cases of familial occurrence of early onset dementia of unknown aetiology. Families with identified mutations should be offered genetic counselling and informed of risks of blood and organs' donation.
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http://dx.doi.org/10.5114/ninp.2012.32353 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany.
Protein misfolding and aggregation are a hallmark of various neurodegenerative disorders. However, the underlying mechanisms driving protein misfolding in the cellular context are incompletely understood. Here, we show that the two-dimensional confinement imposed by a membrane anchor stabilizes the native protein conformation and suppresses liquid-liquid phase separation (LLPS) and protein aggregation.
View Article and Find Full Text PDFMol Neurodegener
December 2024
German Center for Neurodegenerative Diseases (LMU), Klinikum, Germany.
Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Chronic complete spinal cord injury (SCI) is difficult to treat because of scar formation and cavitary lesions. While human iPS cell-derived neural stem/progenitor cell (hNS/PC) therapy shows promise, its efficacy is limited without the structural support needed to address cavitary lesions. Our study investigated a combined approach involving surgical scar resection, decellularized extracellular matrix (dECM) hydrogel as a scaffold, and hNS/PC transplantation.
View Article and Find Full Text PDFAnn Clin Transl Neurol
December 2024
Neurology Department, Albacete Universitary Hospital, Albacete, Spain.
Iatrogenic cerebral amyloid angiopathy, a disease caused by contact with neurosurgical material or human growth hormone contaminated by beta-amyloid peptide (Aβ), has a prion-like transmission mechanism. We present a series of three patients under 55 years of age who underwent cranial surgery. All of them developed multiple cerebral hemorrhages, transient focal neurological deficits, and/or cognitive impairment after 3-4 decades.
View Article and Find Full Text PDFFront Mol Neurosci
December 2024
Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Graduate School of Infectious Diseases, Hokkaido University, Sapporo, Japan.
The accumulation of a disease-specific isoform of prion protein (PrP) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion strain and experimental animal. The brain region-dependent distribution of PrP and neuropathological lesions suggests a neuronal cell-type-dependent prion propagation and vulnerability to prion infection.
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