Cystatin C as a potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt-Jakob disease.
The definite diagnosis of Creutzfeldt-Jakob disease (CJD), the most common form of human prion diseases, relies upon neuropathological data usually obtained at autopsy. In living patients, the diagnosis, based on suggestive clinical features and EEG abnormalities, can be aided by the detection of altered levels of isoforms of the 14-3-3 protein in the cerebrospinal fluid (CSF). However, the validity of this test has been recently challenged and the search for other, more reliable biomarkers for CJD remains highly desirable. The present study describes the identification of a new potential surrogate marker in the CSF of CJD-affected patients. A preliminary study employing surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) technology highlighted a protein at 13.4 kDa in a small group (n = 8) of CJD-affected patients. Further analysis aimed at identifying this protein using cationic exchange chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed it to be cystatin C. Additional immunoblot assays confirmed that the level of cystatin C was significantly increased (p </= 0.05) in all tested samples (n = 8). We conclude that the analysis of cystatin C levels in CSF could be useful as a pre-mortem indicator of the disease.
Sanchez
Jean-Charles
JC
Biomedical Proteomics Research Group, Central Clinical Chemistry Laboratory, Geneva University Hospital, Switzerland. sanchez@sim.hcuge.ch
Guillaume
Elisabeth
E
Lescuyer
Pierre
P
Allard
Laure
L
Carrette
Odile
O
Scherl
Alex
A
Burgess
Jennifer
J
Corthals
Garry L
GL
Burkhard
Pierre R
PR
Hochstrasser
Denis F
DF
D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D055316:Cystatin C; D015891:Cystatins / Q000134:cerebrospinal fluid* / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods
D015415:Biomarkers; C525030:CST3 protein, human; D002556:Cerebrospinal Fluid Proteins; D055316:Cystatin C; D015891:Cystatins