Two-dimensional electrophoresis and "ultrasensitive" silver staining of cerebrospinal fluid proteins in neurological diseases.

Cerebrospinal fluid (CSF) proteins, as resolved by two-dimensional electrophoresis and made visible by silver staining, have been examined in patients with various neurological diseases and normal volunteers. The patterns for 15 of 20 patients with Parkinson's disease showed a protein (Mr 25 000) with charge similar to albumin, which was not seen in the patterns for any of 91 normal volunteers. Patterns for 21 of 22 multiple sclerosis patients showed novel immunoglobulin light chain proteins, also not present in the CSF of any normal volunteers. Quantitative analysis by computer-assisted densitometry in Parkinson's disease and multiple sclerosis showed that 20 of 68 and 33 of 85 proteins, respectively, were significantly altered as compared with proteins in the normal population. This ability to characterize both Parkinson's disease and multiple sclerosis molecularly provides a broad baseline for improved clinical diagnosis and may serve as an aid in exploring the underlying pathophysiology. These studies illustrate the potential of applying this methodology in the study of neurological diseases.