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 (PrP(sen)) to a pathologic form (PrP(res)). The occurrence of a new variant of CJD has increased the demand for a rapid assay capable of detecting a theoretical risk of transmission of the disease by blood or plasma.


METHODS
A quantitative sandwich ELISA for routine screening was developed for analysis of PrP levels in plasma. The time-resolved dissociation-enhanced fluorescence technology allowed a detection limit in plasma samples of approximately 50 pg/mL. Levels of PrP(sen) were tested in plasma from 31 patients with CJD, from 11 patients with other neurodegenerative diseases, and from a control group of 200 healthy subjects.


RESULTS
The assay recognized both PrP(sen) and pathologic PrP(res), but did not differentiate between the two isoforms. PrP(sen) levels were higher in plasma from both patient groups than in plasma from the control group: 27 of the 31 (87%) CJD patients and all patients with other neurodegenerative diseases had higher levels than the highest concentration found in the control group. No correlation was found between age and PrP level. No signal could be detected in the CJD samples after protease K digestion, indicating that all detected PrP was protease-sensitive and therefore not pathologic.


CONCLUSIONS
These data suggest that soluble PrP(sen) in plasma samples might be useful as a surrogate marker for a broad spectrum of neurologic diseases as well as for CJD.
Völkel
D
D
Baxter Hyland Immuno, Vienna, Austria.
Zimmermann
K
K
Zerr
I
I
Bodemer
M
M
Lindner
T
T
Turecek
P L
PL
Poser
S
S
Schwarz
H P
HP
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002648:Child; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000097:blood; D011328:Prions / Q000097:blood* / Q000276:immunology
D015415:Biomarkers; D011328:Prions