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 A beta(1-42)
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 A beta(1-42) levels correlated
negatively with cortical pathology, most clearly with temporal and
occipital lesions. Conclusion: 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.