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Cerebrospinal fluid (CFS) is the most easily accessible component of the human central nervous system and has been successfully used for the analysis of disease-associated molecular imbalances, particularly for extracellular matrix components. Alterations in the presence of the nervous system-associated chondroitin sulfate proteoglycan neurocan had been reported from active multiple sclerosis lesions. Neurocan could be detected as a component of human CFS after enrichment of proteoglycans by anion exchange chromatography from pooled liquor as well as individual 300 μL samples by Western blot. However, a general alteration in neurocan levels in CFS sample with high immunoglobulin content could not be demonstrated. To further reduce the sample size, the development of a PG capturing assay based on polybrene-coated 96-well plates was initiated. This approach could be an interesting alternative option for the analysis of PGs in biological fluid and tissue samples.