Absence of protease-resistant prion protein in the cerebrospinal fluid of Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD), believed to be caused by a protease-resist ant isoform of prion protein (PrPSc), usually manifests itself as a clinica lly distinctive age-related dementia because of its rapid progression, occa sionally accompanied by cerebellar ataxia, Recently a variant CJD (vCJD) ha s been described, which has prominent early psychiatric symptoms and an ear lier age of death. Although cerebrospinal fluid (CSF) is part of the extrac ellular fluid of the central nervous system (CNS), the bulk of its proteins are derived from the plasma and there is increasing concern about possible transmission of prion disease by blood. As investigation of CSF has pla) e d a significant role in the diagnosis and management of several neurologica l diseases, it was decided to characterize PrP present in the CSF of CJD in dividuals. Significant variation was observed in the level of PrP in the CS F from both non-CJD and CJD (including vCJD) patients, and the detected PrP forms are protease-sensitive, Using a conformation-dependent immunoassay, it was further demonstrated that the PrP detected in the CSF from CJD patie nts was broadly similar in conformation to that found in non-CJD patients. Taken together, the results of this study fail to demonstrate any correlati on between the presence of protease-resistant PrP isoform (PrPSc) in the CS F and disease manifestation. Copyright (C) 2001 John Wiley & Sons, Ltd.