CHROMOGRANIN-A IMMUNOREACTIVITY IN HUMAN CEREBROSPINAL-FLUID - PROPERTIES, RELATIONSHIP TO NORADRENERGIC NEURONAL-ACTIVITY, AND VARIATION IN NEUROLOGIC DISEASE

Although measurement of chromogranin A in the bloodstream is of value in sympathoadrenal investigations, little is systematically known abou t chromogranin A in cerebrospinal fluid, despite substantial knowledge about its occurrence and distribution in brain. We therefore applied a homologous human chromogranin A radioimmunoassay to cerebrospinal fl uid, in order to evaluate the properties and stability of cerebrospina l fluid chomogranin A, as well as its relationship to central noradren ergic neuronal activity, to peripheral (plasma) chromogranin A, and to disease states such as hypertension, renal failure and Parkinsonism. Authentic, physically stable chromogranin A immunoreactivity was found in cerebrospinal fluid (at 37-146 ng/ml; mean, 87.0 +/- 6.0 ng/ml in healthy subjects), and several lines of evidence (including 3.39 +/- 0 .27-fold higher chromogranin A in cerebrospinal fluid than in plasma) indicated that it originated from a local central nervous system sourc e, rather than the periphery. Cerebrospinal fluid chromogranin A value s were not influenced by administration of effective antihypertensive doses of clonidine or propranolol, and were not related to the cerebro spinal fluid concentrations of norepinephrine, methoxyhydroxyphenylgly col, or dopamine-beta-hydroxylase; thus, cerebrospinal fluid chromogra nin A was not closely linked to biochemical or pharmacologic indices o f central noradrenergic neuronal activity. Cerebrospinal fluid chromog ranin A was not changed (P > 0. 1) in essential hypertension (84.2 +/- 14.0 ng/ml) or renal failure (72.2 +/- 13.4 ng/ml), despite a marked (7.1-fold; P < 0.001) increase in plasma chromogranin A in renal failu re, and a modest (1.5-fold; P = 0.004) increase in plasma chromogranin A in essential hypertension. In Parkinson's disease, a diminution (2. 8-fold; P < 0.001) of cerebrospinal fluid chromogranin A may be of dia gnostic value.