Clinical proteomics of the cerebrospinal fluid: Towards the discovery of new biomarkers

Abstract

The cerebrospinal fluid (CSF) circulates within the CNS where it plays an essential physiological role in homeostasis of neuronal cells. This biological fluid has an important protein diversity that results from both filtration of serum through the blood-brain barrier and production/secretion of neuronal peptides and proteins. Changes in CSF composition depend on blood proteome, CSF circulation alterations, as well as physiological or pathological brain status. Hence, CSF proteomic analysis gives a unique opportunity to detect and describe biomarkers in neurological affections. Although lumbar puncture is considered as invasive, post lumbar puncture events remain rare and minor. Nevertheless, CSF biological analysis is currently limited to a small number of parameters and clinical situations suggesting mainly meningitis, malignancies or dementia. Few CSF proteomic studies have been performed in comparison to those on blood. In this review, we will provide a proteomics description of the CSF, summarize the current clinical use of this fluid and describe its clinical proteomics examination.

Comparative peptidome analyses of the profiles of the peptides ranging from 1­–10 KD in CSF samples pooled from probable sporadic CJD and non-CJD patients

“…Being multiple lengths of cellular proteins in body fluids is a common phenomenon, which represents a regular metabolism process of protein or a degradation situation of protein during cell lysis. 15 Interestingly, the signals of several neurodegeneration-associated proteins, such as glial fibrillary acidic protein (GFAP) and apolipoprotein E (ApoE), even 14-3-3 protein, have been also identified in this fraction, but not limiting to the CSF samples of probable sCJD, which may indicate a common phenomenon of metabolism of cellular proteins in neurodegeneration.…”

Two-Dimensional Gel Electrophoresis (2-DE)

“…A prefractionation step, such as depletion of a few high-abundant proteins, can assist in the detection of less abundant proteins that may be informative biomarkers (Björall K et al, 2005). The same problem may arise from other biological fluids such as cerebrospinal fluid (CSF), as rich in albumin as serum (Roche, 2008). Negative staining with imidazole zinc is an alternative for staining with good sensitivity (15 ng per spot) as only the background is stained, and not the proteins; but it cannot be used for quantification.…”

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

“…The cerebrospinal fluid (CSF) is an interesting target for human biomarker studies in neurological disorders [204].…”

“…The total protein concentration in CSF is about 0.5% of that in plasma [53,113,164,204]. Diffusion of proteins from blood to CSF is restricted directly by the Blood-CSF Barrier (BCB) located in the choroid plexus and arachnoid granulations, but also indirectly by the BBB which is present along almost all of the brain's capillaries (the exception being the socalled circumventricular organs of the brain) [53,105].…”