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. Copyright (C) 2007 S. Karger AG, Basel.