Specific and surrogate cerebrospinal fluid markers in Creutzfeldt–Jakob Disease (chapter 17)

Detection of cerebrospinal fluid (CSF) biomarkers is a major challenge for laboratories involved in neurological disorder diagnostics and the long list of putative markers now available reflects the enormous efforts and the relevance of CSF in neurology. The result of these intensive studies on CSF is that specific biomarkers are included as supportive criteria for neurodegenerative disorder diagnosis. The diagnostic strategies for biomarkers detection include the detection of surrogate markers which act as bystanders of an ongoing pathogenic process or of those distinct proteins involved in the pathogenic mechanisms. Creutzfeldt–Jakob represents an example in which a surrogate marker such as 14-3-3 had been included among the diagnostic criteria. However, 14-3-3 protein is a very sensitive marker which might indicate positive in several neurological conditions thus reducing its specificity, and it is now coupled with elevated Tau protein levels (>1,300 pg/ml) reaching a specificity of around 100%. This indicates that the aim of CSF diagnostics, not only in sCJD but more widely in different neurodegenerative disorders, is focused on the combination of different CSF biomarkers, resulting in up- or down-regulation in a distinct neurological disorder, in order to increase the specificity and sensibility. Here, we show a series of biomarkers modified in sCJD and the biochemical methods applicable for the detection of novel biomarkers in the CSF, as well as future perspectives for novel biomarkers detection in the CSF.