Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum

In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q(10) (CoO10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ(10) biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ(10) deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ(10). To investigate whether CoQ(10) deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ(10) levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ(10) deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ(10) in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ(10) deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ(10) levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.