Immunochemical determination of cellular prion protein in plasma from healthy subjects and patients with sporadic CJD or other neurologic diseases

BACKGROUND: Creutzfeldt-Jakob disease is thought to be caused by conversion of cellular prion protein (PrP) from its soluble form (PrPsen) to a pathol ogic form (PrPres). The occurrence of a new variant of CJD has increased th e demand for a rapid assay capable of detecting a theoretical risk of trans mission of the disease by blood or plasma. STUDY DESIGN AND METHODS: A quantitative sandwich ELISA for routine screeni ng was developed for analysis of PrP levels in plasma. The time-resolved di ssociation-enhanced fluorescence technology allowed a detection limit in pl asma samples of approximately 50 pg/mL. Levels of PrPsen were tested in pla sma from 31 patients with CJD, from 11 patients with other neurodegenerativ e diseases, and from a control group of 200 healthy subjects. RESULTS: The assay recognized both PrPsen and pathologic PrPres, but did no t differentiate between the two isoforms. PrPsen levels were higher in plas ma from both patient groups than in plasma from the control group: 27 of th e 31 (87%) CJD patients and all patients with other neurodegenerative disea ses had higher levels than the highest concentration found in the control g roup. No correlation was found between age and PrP level. No signal could b e detected in the CJD samples after protease K digestion, indicating that a ll detected PrP was protease-sensitive and therefore not pathologic. CONCLUSION: These data suggest that soluble PrPsen in plasma samples might be useful as a surrogate marker for a broad spectrum of neurologic diseases as well as for CJD.