MM2-Thalamic Creutzfeldt-Jakob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain
| Autor: | Fabrizio Tagliavini, Robert G. Will, Jan P. M. Langeveld, Chiara Vimercati, Fabio Moda, Silvia Suardi, Giuseppe Di Fede, Giorgio Giaccone, Antonio Brambilla, Jean Manson, Ilaria Campagnani, Pietro Zerbi, Margherita Ruggerone, Paolo Fociani, Alessandro Terruzzi, Matthew Bishop, Lucia Limido, Antonio Indaco |
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| Rok vydání: | 2012 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty medicine.diagnostic_test animal diseases General Neuroscience Thalamus Creutzfeldt�Jakob disease Scrapie Biology medicine.disease Phenotype Virology nervous system diseases Pathology and Forensic Medicine medicine.anatomical_structure Gliosis Western blot Cerebral cortex mental disorders medicine Neurology (clinical) medicine.symptom |
| Zdroj: | Brain Pathology. 22:662-669 |
| ISSN: | 1015-6305 |
| Popis: | In CreutzfeldtJakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrPSc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrPSc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrPSc. Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrPSc, a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. |
| Databáze: | OpenAIRE |
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