Proteomic analysis of the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.
So far, only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) has been accepted as diagnostic criterion for Creutzfeldt-Jakob disease (CJD). However, this assay cannot be used for screening because of the high rate of false-positive results, whereas patients with variant CJD are often negative for 14-3-3 proteins. The aim of this study was to compare the spot patterns of CSF by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to search for a CJD-specific spot pattern. We analyzed the CSF of 28 patients [11 CJD, 9 Alzheimer's disease (AD), 8 nondemented controls (NDC)] employing 2D-PAGE which was optimized for minimal volumes of CSF (0.1 ml; 7-cm strips). All samples were run at least three times, gels were silver stained and analyzed by an analysis software and manually revised. We could consistently match 268 spots which were then compared between all groups. By the use of 5 spots, we were able to differentiate CJD from AD or NDC with a sensitivity of 100%. CJD could also be distinguished from both groups by using a heuristic clustering algorithm of 2 spots. We conclude that this proteomic approach can differentiate CJD from other diseases and may serve as a model for other neurodegenerative diseases.
Cepek
Lukas
L
Department of Neurology, University of Ulm, Ulm, Germany.
Brechlin
Peter
P
Steinacker
Petra
P
Mollenhauer
Brit
B
Klingebiel
Enrico
E
Bibl
Mirko
M
Kretzschmar
Hans A
HA
Wiltfang
Jens
J
Otto
Markus
M
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000368:Aged; D000369:Aged, 80 and over; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid; D040901:Proteomics / Q000379:methods*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D012680:Sensitivity and Specificity; D013129:Spinal Puncture; D016875:tau Proteins / Q000134:cerebrospinal fluid
D048948:14-3-3 Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D016875:tau Proteins