Affiliations: Proteomics, Finnigan Mass Spectrometry, Thermo
Electron, San Jose, CA 95134, USA | Molecular Neurology Program, Huntington Medical
Research Institutes. Pasadena, CA 91101, USA
Note: [] Corresponding author: Andreas F. Hühmer, PhD., Proteomics,
Finnigan Mass Spectrometry, San Jose, CA 95134, USA. Tel.: +1 408 965 6000;
E-mail: andreas.huhmer@thermo.com
Abstract: The introduction of lumbar puncture into clinical medicine over 100
years ago marks the beginning of the study of central nervous system diseases
using the human cerebrospinal fluid (CSF). Ever since, CSF has been analyzed
extensively to elucidate the physiological and biochemical bases of
neurological disease. The proximity of CSF to the brain makes it a good target
for studying the pathophysiology of brain functions, but the barrier function
of the CSF also impedes its diagnostic value. Today, measurements to determine alterations in the composition of
CSF are central in the differential diagnosis of specific diseases of the
central nervous system (CNS). In particular, the analysis of the CSF protein
composition provides crucial information in the diagnosis of CNS diseases. This
enables the assessment of the physiology of the blood-CSF barrier and of the
immunology of intrathecial responses. Besides those routine measurements,
protein compositional studies of CSF have been extended recently to many other
proteins in the expectation that comprehensive analysis of lower abundance CSF
proteins will lead to the discovery of new disease markers. Disease marker
discovery by molecular profiling of the CSF tissue has the enormous potential
of providing many new disease relevant molecules. New developments in protein
profiling techniques hold promise for the discovery and validation of relevant
disease markers. In this review, we summarize the current efforts and progress
in CSF protein profiling measurements using conventional and current protein
analysis tools. We also discuss necessary development in methodology in order
to have the highest impact on the study of the molecular composition of CSF
proteins.
