Identification of Brain Cell Death Associated Proteins in Human Post-mortem Cerebrospinal Fluid

Following any form of brain insult, proteins are released from damaged tissues into the cerebrospinal
fluid (CSF). This body fluid is therefore an ideal sample to use in the search for biomarkers of
neurodegenerative disorders and brain damage. In this study, we used human post-mortem CSF as a
model of massive brain injury and cell death for the identification of such protein markers. Pooled
post-mortem CSF samples were analyzed using a protocol that combined immunoaffinity depletion of
abundant CSF proteins, off-gel electrophoresis, SDS-PAGE and protein identification by LC−MS/MS.
A total of 299 proteins were identified, of which 172 proteins were not previously described to be present
in CSF. Of these 172 proteins, more than 75% have been described as intracellular proteins suggesting
that they were released from damaged cells. Immunoblots of a number of proteins were performed
on individual post-mortem CSF samples and confirmed elevated concentrations in post-mortem CSF
compared to ante-mortem CSF. Interestingly, among the proteins specifically identified in the post-mortem CSF, several have been previously described as biochemical markers of brain damage.
Keywords: brain damage • neurodegeneration • neurodegenerative disease • cerebrospinal fluid • biomarker