NR ATJT
AU Miele,G.; Seeger,H.; Eberhard,R.; Marino,D.; Heikenwälder,M.; Hock,C.; Glatzel,M.; Aguzzi,A.
TI Secreted preclinical biomarkers of prion infection
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Diagnosis DIA-05
PT Konferenz-Poster
AB Prion infections result in progressive fatal neurodegeneration whose molecular underpinnings are not fully understood. Medical interventions, possibly including blood transfusions, have resulted in human-to-human transmission of prions. However, there are no effective therapies, and no suitable biomarkers are available, neither for preclinical laboratory diagnosis of prion infection in body fluids, monitoring efficacy of future therapeutic regimens or premortem screening regimens in animals. Using high-density oligonucleotide arrays we performed global gene expression studies of CNS tissue during the presymptomatic phase of prion infection in a murine model of scrapie, focusing on those genes appearing upregulated and which code for secretory proteins. We found that two cysteine protease inhibitors undergo profound transcriptional upregulation in the central nervous system of preclinically infected mice. We then studied the homologous transcripts in human prion diseases and other neurodegenerative conditions. Both mRNAs were upregulated in Creutzfeldt-Jakob disease (CJD) and, to a lesser extent, in Alzheimer' disease (AD) brains. Both transcripts encode secretory signal peptides, their gene products are secreted and known to be present in a variety of body fluids. Besides suggesting a previously unrecognized role for these protease inhibitors in prion pathogenesis, these novel biomarkers may be useful for monitoring the efficacy of therapeutic regimens and possibly for preclinical laboratory diagnostics of prion infections in humans and animals. Progress in our efforts to determine the usefulness of these biomarkers will be presented.
AD G.Miele, H.Seeger, R.Eberhard, D.Marino, M.Heikenwälder, M.Glatze, A.Aguzzi, Institute of Neuropathology, University Hospital Zürich, Zürich, Switzerland; C.Hock, Division of Psychiatry Research, University of Zürich, Zürich, Switzerland
SP englisch
PO Deutschland