Proteomic screening of cerebrospinal fluid: candidate proteomic biomarkers for sample stability and experimental autoimmune encephalomyelitis

PhD ceremony: Ms. A.T.I. Rosenling, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Title: Proteomic screening of cerebrospinal fluid: candidate proteomic biomarkers for sample stability and experimental autoimmune encephalomyelitis

Promotor(s): prof. R.P.H. Bischof

Faculty: Mathematics and Natural Sciences

Cerebrospinal fluid (CSF) is one of the most promising compartments when it comes to the search for biomarkers that are related to neurological disorders. One disease affecting the central nervous system is multiple sclerosis (MScl). Diagnosing the disease is cumbersome, the cause unknown and treatment is only disease modifying; there is no cure. To reduce relapse rate and severity and to minimize disability, it is of importance to detect the disease at an early stage. The discovery of specific and reliable molecular biomarkers would be of great importance in this respect.

Part of the studies described in this thesis, were designed to discover proteomic biomarkers that are related to MScl, by screening CSF using mass spectrometry-based analysis methods. The studies are based on the experimental autoimmune encephalomyelitis (EAE) rat model, which mimics certain aspects of MScl. Even though animal models will never completely copy the complexity of the human disease, animal studies allow to follow the course of disease in a more controlled manner by reducing biological variation, which increases the likelihood to detect disease-related markers.

In the search for biomarkers it is of importance to exclude artifacts introduced by sample handling. This thesis studies the effect of storage temperature and number of freeze-thaw cycles on the proteome/metabolome of CSF, with the goal to define the boundaries of appropriate sample handling for molecular biomarker studies.

The studies revealed a number of proteins/peptides and metabolites that were affected by sample handling and several candidate proteomic biomarkers were discovered having a connection to EAE.