Coenzyme Q10 levels are reduced in the cerebellum of multiple system atrophy patients (P1.182)

BACKGROUND: Multiple system atrophy (MSA) is an incurable neurodegenerative condition. COQ2 is a gene that encodes for an enzyme that participates in the synthetic pathway of Coenzyme Q10 (CoQ10), the predominant coenzyme Q in humans. Through linkage-analysis and whole-genome-sequencing, variants in COQ2 have been linked to clinically diagnosed Japanese MSA patients in a multicenter study. The authors of that study, by analyzing a small sample, suggested decreased levels of CoQ10 in brain tissue of MSA cases. We were unable to replicate the genetic finding. However, in view of the brain tissue result, we decided to investigate further the role of the CoQ10 pathway. We determined the level of CoQ10 in brain tissue from pathologically confirmed MSA cases and compared these levels to those of normal controls as well as to other neurodegenerative disorders.METHODS: Flash-frozen brain tissue of 22 pathologically confirmed MSA patients [9 olivopontocerebellar-atrophy (OPCA) type, 6 striatonigral-degeneration type, and 6 mixed type] was used for this study. Elderly controls (n=37) as well as Idiopathic Parkinson9s disease (IPD;n=7), dementia with Lewy bodies (DLB;n=20), corticobasal degeneration (CBD;n=15) and cerebellar degeneration (CD;n=7) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high-performance-liquid-chromatography.RESULTS: We detected a statistically significant reduction in the levels of CoQ10 in the cerebellum of MSA cases (P=0.002), specifically in OPCA (Pu003c0.001) and mixed cases (P=0.016), when compared to controls as well as to other neurodegenerative diseases [DLB (Pu003c0.001), IPD (P=0.002), CBD (P=0.001), and CD (P=0.032)].CONCLUSION: Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is likely involved in the pathogenesis of MSA but the specificity of this finding remains to be elucidated.Study supported by:The authors are grateful to the MRC-UK, The Wellcome Trust, the MSA-Trust and the NIHR-UCLH-BRC for funding this work. Disclosure: Dr. Schottlaender has nothing to disclose. Dr. Bettencourt has nothing to disclose. Dr. Kiely has nothing to disclose. Dr. Chalasani has nothing to disclose. Dr. Neergheen has nothing to disclose. Dr. Holton has nothing to disclose. Dr. Hargreaves has nothing to disclose. Dr. Houlden has nothing to disclose.