Cerebrospinal fluid (CSF) contains a dynamic and complex mixture of proteins, which reflects physiologic or pathologic states of the central nervous system. Changes in CSF proteome have been described in various neurodegenerative disorders. Earliest publications came from the field of prion disease. Two major approaches have been followed aiming to detect the pathologic 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. First observations were made using two-dimensional gel electrophoresis for proteins named p130/131, identified as belonging to the 14-3-3 protein family group. This protein became known as the first "wet" biomarker part of clinical diagnostic criteria. Other proteins were identified; most of the work in addition to 14-3-3 has been done on tau/p-tau. The development of PrPSc-based biomarkers was hampered by technical problems and detection limits. A novel technique which uses an amplification procedure followed by an aggregation step (real-time quaking-induced conversion: RT-QuIC) emerged and allows the detection of abnormally folded PrPSc in the CSF. This chapter summarizes the current knowledge of biomarker development in prion disease and discusses perspectives for new approaches.
Keywords: 14-3-3; 2D gel electrophoresis; Abeta; PrPSc; RT-QuIC; cytokines; prion; proteomics; synuclein; tau.
Copyright © 2017 Elsevier B.V. All rights reserved.