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Biochemical Markers in CSF of ALS Patients

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Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron diseases (MND) characterized by progressive selective degeneration of motor neurons. Although several mutations underlying rare cases of familial ALS were identified during the last decade, the pathogenesis of ALS remains poorly understood. Various mechanisms have been suggested to contribute to disease pathology such as excitotoxicity, oxidative stress, protein aggregation, and inflammation. Accordingly, several candidate biochemical markers related to these pathomechanisms were investigated in cerebrospinal fluid (CSF). Although none of these markers gained clinical importance so far, CSF might reflect pathophysiological alterations in the course of the disease and could therefore provide an insight into pathomechanisms in vivo. It is suggested that cellular and proteinchemical processes are better reflected in the CSF than in other body fluids such as blood or urine due to the proximity of the affected motor neurons to the CSF compartment. Accordingly, alterations in protein expression, post-translational modification or turnover within the tissue of the central nervous system may be mirrored in corresponding changes in CSF protein content. Research on biomarkers in CSF using novel discovery technologies such as proteomics allows to search for a set of proteins that reflect different disease specific molecular pathways and might therefore be of relevance for the establishment of biomarkers for therapeutic monitoring and the development of novel therapies. In this review, an updated overview is given on CSF biomarkers related to the pathomechanisms supposed to be participating in the complex disease process of ALS.

Keywords: Amyotrophic lateral sclerosis; biochemical marker; biological marker; cerebrospinal fluid; motor neuron disease; proteomics

Document Type: Research Article


Affiliations: Department of Neurology, University of Ulm, Director CSF Laboratory, Oberer Eselsberg 45, D-89081 Ulm, Germany.

Publication date: 2008-08-01

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