NR ARSR
AU Safar,J.G.; Geschwind,M.D.; Deering,C.; Didorenko,S.; Sattavat,M.; Sanchez,H.; Serban,A.; Vey,M.; Baron,H.; Giles,K.; Miller,B.L.; DeArmond,S.J.; Prusiner,S.B.
TI Diagnosis of human prion disease
QU Proceedings of the National Academy of Sciences of the United States of America 2005 Mar 1; 102(9): 3501-6
IA http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=552933&blobtype=pdf
PT journal article
AB With the discovery of the prion protein (PrP), immunodiagnostic procedures were applied to diagnose Creutzfeldt-Jakob disease (CJD). Before development of the conformation-dependent immunoassay (CDI), all immunoassays for the disease-causing PrP isoform (PrPsc) used limited proteolysis to digest the precursor cellular PrP (PrPc). Because the CDI is the only immunoassay that measures both the protease-resistant and protease-sensitive forms of PrPsc, we used the CDI to diagnose human prion disease. The CDI gave a positive signal for PrPsc in all 10-24 brain regions (100%) examined from 28 CJD patients. A subset of 18 brain regions from 8 patients with sporadic CJD (sCJD) was examined by histology, immunohistochemistry (IHC), and the CDI. Three of the 18 regions (17%) were consistently positive by histology and 4 of 18 (22%) by IHC for the 8 sCJD patients. In contrast, the CDI was positive in all 18 regions (100%) for all 8 sCJD patients. In both gray and white matter, approximately 90% of the total PrPsc was protease-sensitive and, thus, would have been degraded by procedures using proteases to eliminate PrPc. Our findings argue that the CDI should be used to establish or rule out the diagnosis of prion disease when a small number of samples is available as is the case with brain biopsy. Moreover, IHC should not be used as the standard against which all other immunodiagnostic techniques are compared because an immunoassay, such as the CDI, is substantially more sensitive.
MH Biopsy; Brain/metabolism/pathology; Codon; Creutzfeldt-Jakob Syndrome/*diagnosis/genetics/metabolism; Female; Humans; Middle Aged; Polymorphism, Genetic; PrPsc Proteins/genetics/metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Sensitivity and Specificity
AD Jiri G. Safar, Camille Deering, Svetlana Didorenko, Ana Serban, Kurt Giles, Stephen J. DeArmond, Stanley B. Prusiner, Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA; Michael D. Geschwind, Bruce L. Miller, Memory and Aging Center, University of California, San Francisco, CA 94143, USA; Jiri G. Safar, Michael D. Geschwind, Kurt Giles, Bruce L. Miller, Stanley B. Prusiner, Department of Neurology, University of California, San Francisco, CA 94143, USA; Mamta Sattavat, Henry Sanchez, Stephen J. DeArmond, Department of Pathology, University of California, San Francisco, CA 94143, USA; Jiri G. Safar, Ana Serban, Kurt Giles, Stephen J. DeArmond, Stanley B. Prusiner, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA; Martin Vey, ZLB Behring, 35041 Marburg, Germany; Henry Baron, ZLB Behring, 75601 Paris, France
SP englisch
PO USA