Brain-derived proteins in the CSF: do they correlate with brain pathology in CJD?
BACKGROUND
Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Abeta1-42 were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed.


METHODS
CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients.


RESULTS
We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrPc) and Abeta1-42 levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions.


CONCLUSIONS
Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins.
Boesenberg-Grosse
Constanze
C
National Reference Center for TSE Surveillance, Dept. of Neurology, Georg-August-University Göttingen, Robert-Koch-Str, 40, 37075 Göttingen, Germany. ynnoc2001@web.de
Schulz-Schaeffer
Walter J
WJ
Bodemer
Monika
M
Ciesielczyk
Barbara
B
Meissner
Bettina
B
Krasnianski
Anna
A
Bartl
Mario
M
Heinemann
Uta
U
Varges
Daniela
D
Eigenbrod
Sabina
S
Kretzschmar
Hans A
HA
Green
Alison
A
Zerr
Inga
I
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D011328:Prions / Q000134:cerebrospinal fluid; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
D048948:14-3-3 Proteins; D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D011328:Prions; D009418:S100 Proteins; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase