Prion Diseases pp 229-252 | Cite as

Biomarkers in Cerebrospinal Fluid

  • Joanna Gawinecka
  • Matthias Schmitz
  • Inga ZerrEmail author
Part of the Neuromethods book series (NM, volume 129)


Cerebrospinal fluid (CSF) is the main component of the brain extracellular space and participates in the exchange of many biochemical products in the central nervous system (CNS). Consequently, CSF contains a dynamic and complex mixture of proteins, which reflects physiological or pathological state of CNS. Changes in CSF proteome have been described in various neurodegenerative disorders. These alterations are also discussed to reflect pathological changes in the brain and thus contribute to a better understanding of the pathophysiology of the underlying disorder.

Proteomics offer a new methodology for the analysis of pathological changes and mechanisms occurring in neurodegenerative processes and provide a possibility of novel biomarker discovery to supplement faster, earlier, and precise diagnosis. In general, following criteria have to be applied in order to qualify a protein or a gene as a potential biomarker: the selected parameters have to be sensitive (able to detect the abnormalities in early stage of disease), specific (allow the differential diagnosis), reproducible across different laboratories, with high positive predictive value (indicate the disease when test is positive) and allow the disease monitoring as well as a potential therapy response. In Creutzfeldt–Jakob disease, two major lines of approaches have been followed aiming to detect the pathological form of prion protein (PrPSc) in various peripheral tissues on one hand, but also looking for surrogate parameters as a consequence of the underlying neurodegenerative process. While the amounts of the abnormal disease-related PrPSc in CSF and blood in human TSEs seem to be extremely low, the development of PrPSc-based biomarker was hampered by technical problems and the detection limits. On the other hand, a variety of other proteins have been investigated in the CSF and recently a variety of potential biomarkers have been reported, which contribute to the clinical diagnosis. Already established biomarkers are 14-3-3, β-amyloid, tau-protein and phosphorylated tau isoforms, S100b, as well as neuron-specific enolase (NSE). Since some of these markers display certain limitations, the search continues. The review summarizes the current knowledge of the biomarker development in prion diseases and discusses perspectives for new approaches.

Key words

TSE CJD 14-3-3 Tau CSF Biomarker Proteomics RT QuIC 


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© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of NeurologyClinical Dementia Center, National Reference Center for TSE, Georg-August UniversityGöttingenGermany

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