Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

Abstract

BackgroundThe objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases.MethodsFlash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography.ResultsWe detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson's disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)].ConclusionOur results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated.

Understanding Multiple System Atrophy—Could Genetics Lead the Way?

“…The pathogenesis of MSA remains an enigma, though it is becoming clear that genetic associations exist. Many mechanisms for the development and propagation of MSA have been postulated, including impaired elimination of α-synuclein within the cell, [41][42][43][44] mitochondrial dysfunction, 32,33,45,46 direct toxicity of α-synuclein, 47 oxidative stress, 48 and neuroinflammation. 49,50 More recently, there are also data that implicate a prion-like propagation of MSA.…”

“…[26][27][28][29][30][31] Further studies have revealed reduction in CoQ10 levels in the cerebellum and serum of patients with MSA. 32,33 These findings may be particularly important in implicating CoQ10 supplementation as a therapeutic option in MSA, though this has not yet been systematically studied.…”

Coenzyme Q10 as a Peripheral Biomarker for Multiple System Atrophy

“…9 Therefore, the rare patients with MSA and COQ2 mutations may be regarded as having an adult-onset variant of primary CoQ10 deficiency without prominent ophthalmologic or renal involvement. By contrast, individuals with sporadic MSA show a selective decrease of levels of CoQ10 in the cerebellum, 10,11 potentially owing to environmental, genetic or epigenetic, and other factors influencing CoQ10 biosynthetic pathways. A study of enzyme levels in the CoQ10 biosynthetic pathways revealed that levels of PDSS1 and COQ5, but not other CoQ10-synthesizing enzymes, are selectively decreased in the cerebellum of patients with MSA.…”

“…1 These molecular findings have revealed the importance of the CoQ10 biosynthetic pathway in MSA and raise the question: is CoQ10 deficiency also present in the brains of patients with sporadic MSA because of a shared disease mechanism between genetic and sporadic MSA? To address this issue, Schottlaender et al 10 found that patients with sporadic MSA have decreased levels of CoQ10 in the cerebellum but normal levels in the frontal cortex when compared with controls. In addition, one study observed that patients with MSA without COQ2 mutations have 40% lower levels of CoQ10 in the cerebellum compared with controls, whereas the occipital cortex has normal levels of CoQ10.…”

“…14,15 In these disorders, mitochondrial functions are compromised; however, there is no evidence of CoQ10 deficiency, since levels of CoQ10 are normal in the brains of patients with Parkinson disease 10,11 and in the cerebellum of patients with Friedreich ataxia. 10 Mitochondria are responsible for many important biological functions; therefore, CoQ10 might not be able to rescue mitochondrial defects specific to Parkinson disease or Friedreich ataxia. On the other hand, the genetic evidence along with results of postmortem brain examinations and studies of peripheral blood biomarkers consistently indicate that CoQ10 might play a major role in MSA.…”