Cerebellar α-Ketoglutarate dehydrogenase activity is reduced in spinocerebellar ataxia type 1

We measured the activity of the thiamine pyrophosphate–dependent enzyme α-ketoglutarate dehydrogenase complex in postmortem brain of 12 patients with the spinocerebellar ataxia type 1 form of olivopontocerebellar atrophy. α-Ketoglutarate dehydrogenase complex activity measured in the absence of thiamine pyrophosphate was markedly reduced (−72%) in olivopontocerebellar atrophy cerebellar cortex. Decreased activity of this key rate-limiting Krebs cycle enzyme could compromise cerebellar energy metabolism and excitatory amino acid synthesis and thereby contribute to the brain dysfunction of olivopontocerebellar atrophy.