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Human transmissible spongiform encephalopathies

Ziel

To monitor the Europe-wide incidence of neuropathologically confirmed human transmissible spongiform encephalopathies (TSEs, prion diseases) both prospectively and retrospectively.
To monitor the clinicopathological pattern of human TSEs in Europe and possible emergence of new patterns.
To characterise the range of the phenotypic spectrum of human TSEs, with emphasis on detailed neuropathological assessment. In particular, the new variant of CJD will be searched both prospectively and retrospectively on a Europe-wide scale. Moreover, this neuropathological assessment might serve as basis for a redefinition of criteria for diagnosis and classification of human TSEs.
To further characterise the link between human TSE phenotypes and the genotype of the prion protein (PrP) gene (PRNP) by assessing the distribution of PRNP mutations and relevant polymorphisms in Europe.
To clarify the pathogenesis of tissue damage in human TSEs, especially the relation of PrP deposition and tissue lesioning.
To further characterise other neurodegenerative conditions suspected as prion diseases such as progressive subcortical gliosis.
To develop improved diagnostic tools, including antibodies which might be able to discriminate between the normal and the pathological isoforms of PrP, and a standard for laboratory diagnostics of TSEs.

TSEs represent a unique paradigm in biomedicine: they can be both infectious and hereditary, with the intriguing "prion" hypothesis of infectivity conferred by a proteinase resistant (prion) protein (PrP) only. Moreover, world-wide concern has been emerging about a link between human diseases and those in animals, most notably bovine spongiform encephalopathy (BSE). For a most recently recognised new variant of Creutzfeldt-Jakob disease (nv-CJD) in the UK and France, origin from BSE has become probable. Human TSEs can be definitely diagnosed only by neuropathological examination. For diagnosis of nv-CJD, autopsy confirmation is mandatory. This project aims to gain further insight into the various phenotypes of human TSEs, their distribution and pathogenesis. Coordination of its tasks will exploit the infrastructure of a European network of laboratories involved in diagnosis of, and basic research in, human TSEs. The European database of human TSEs, the Tissue Bank, and the Clearing House for atypical cases will be expanded and supplemented by additional research into PRNP genotypes and pathogenesis of CNS tissue lesions, and by development of improved diagnostic tools such as new antibodies.

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Koordinator

Universität Wien
EU-Beitrag
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Adresse
18-20,Wahringer Gürtel
1097 WIEN
Österreich

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