Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive motor neuron degeneration. Currently, disease management is hindered by a lengthy diagnostic process which is based heavily on clinical criteria. A reliable panel of biomarkers is needed in order to accelerate the diagnosis of this disease and aid in monitoring its progression. We have previously reported proteomic evidence supporting a reduction of Cystatin C protien levels in the cerebrospinal fluid (CSF) of ALS patients relative to controls. In this study, we have evaluated the potential of Cystatin C as a diagnostic and/or prognostic biomarker by assessing its expression over the course of disease progression. We used a quantitative ELISA to evaluate Cystatin C concentration in both CSF and plasma at multiple time points following ALS symptom onset. Cystatin C levels in both fluids were found to correlate strongly with clinical measures of disease progression. This correlation was maintained during transient functional improvements observed in some patients during drug trial participation. Additionally, expression patterns were observed to vary between specific subpopulations of ALS patients. These data support the utility of Cystatin C as both a diagnostic biomarker and a surrogate biomarker for monitoring disease progression and treatment response.Funded by: University of Pittsburgh Center for ALS Research
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