CEREBELLAR ALPHA-KETOGLUTARATE DEHYDROGENASE-ACTIVITY IS REDUCED IN SPINOCEREBELLAR ATAXIA TYPE-1

We measured the activity of the thiamine pyrophosphate-dependent enzym e alpha-ketoglutarate dehydrogenase complex in postmortem brain of 12 patients with the spinocerebellar ataxia type 1 form of olivopontocere bellar atrophy. alpha-Ketoglutarate dehydrogenase complex activity mea sured in the absence of thiamine pyrophosphate was markedly reduced (- 72%) in olivopontocerebellar atrophy cerebellar cortex. Decreased acti vity of this key rate-limiting Krebs cycle enzyme could compromise cer ebellar energy metabolism and excitatory amino acid synthesis and ther eby contribute to the brain dysfunction of olivopontocerebellar atroph y.