Abnormalities of neurotransmitter enzymes in Huntington's chorea.

The activities of L-glutamate decarboxylase (GAD), GABA-transaminase (GABA-T), choline acetyltransferase (CAT), and cysteic and cysteinesulfinic acids decarboxylase (CAD/CSAD) in putamen and frontal cortex in both Huntington's chorea and normal tissues were measured. The greatest difference between Huntington's and normal tissues occurred in putamen, in which the apparent CSAD activity was reduced by 85%, while no difference was observed in frontal cortex. GAD, CAD, and CAT activities were also reduced in putamen by 65%, 63%, and 42%, respectively (P less than 0.05). Slight reduction in the enzyme activities was also observed in frontal cortex. However, these reductions appeared to be statistically insignificant (P greater than 0.05 in all cases). GABA-T showed little difference in both putamen and frontal cortex in Huntington's chorea and normal tissues. GAD and GABA-T from Huntington's tissues were indistinguishable from those obtained from normal tissues by double diffusion test and by microcomplement fixation test, which is capable of distinguishing proteins with a single amino acid substitution. Furthermore, the similarity of the complement fixation curves for GAD from Huntington's and normal tissues suggests that the decrease in GAD activity is probably due to the reduction in the number of GAD molecules, presumably through the loss of neurons, and not due to the inhibition or inactivation of GAD activity by toxic substances which might be present in Huntington's chorea.