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.