LEVELS AND PROTEOLYTIC PROCESSING OF CHROMOGRANIN-A AND CHROMOGRANIN-B AND SECRETOGRANIN-II IN CEREBROSPINAL-FLUID IN NEUROLOGICAL DISEASES

Human cerebrospinal fluid (CSF) contains chromogranin A and B and secr etogranin II which represent peptides secreted from neuronal large den se core vesicles. Within these vesicles these precursor peptides are a t least partly processed to smaller peptides. We analysed the CSF leve ls of chromogranins/secretogranin by radioimmunoassay using specific a ntisera. The degree of their processing was characterized by molecular sieve column chromatography followed by radioimmunoassay. As previous ly shown secretogranin II is fully processed to smaller peptides inclu ding the peptide secretoneurin, whereas processing of chromogranin A w as more limited. For chromogranin B we found in this study a high degr ee of processing comparable to that of secretogranin II. An analysis o f CSF from patients with multiple sclerosis, essential tremor, Alzheim er and Parkinson disease? did not reveal any differences in proteolyti c processing of chromogranins/secretogranin when compared to control C SF. We conclude that in the four diseases investigated there is no cha nge in the proteolytic processing of the chromogranins/secretogranin w ithin the large dense core vesicles. The absolute levels of chromogran ins/secretogranin varied in CSF collected in different hospitals, howe ver their relative ratios were remarkable constant. We suggest to use this ratio as a parameter to standardise CSF levels of other peptides, e.g. neuropeptides. In Parkinson patients the chromogranin A/secretog ranin II ratio was significantly increased whereas in Alzheimer patien ts and those with essential tremor and multiple sclerosis no change of the ratios was observed. Apparently there are only limited changes in the biosynthesis, processing. secretion and CSF clearance of these pe ptides ill pathological conditions.