Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2'-deoxyguanosine in the CSF of patients with Alzheimer's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process

J Neurol. 2010 Mar;257(3):399-404. doi: 10.1007/s00415-009-5333-x. Epub 2009 Sep 27.

Abstract

To investigate the possibility that mitochondrial oxidative damage, oxidative DNA damage or both contribute to the neurodegenerative process of Alzheimer's disease (AD), we employed high-performance liquid chromatography using an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q-10 (CoQ-10) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 30 patients with AD and in 30 age-matched controls with no neurological disease. The percentage of oxidized/total CoQ-10 (%CoQ-10) in the CSF of the AD group (78.2 +/- 18.8%) was significantly higher than in the control group (41.3 +/- 10.4%) (P < 0.0001). The concentration of 8-OHdG in the CSF of AD patients was greater than in the CSF of controls (P < 0.0001) and was positively correlated with the duration of illness (r(s) = 0.95, P < 0.0001). The %CoQ-10 was correlated with concentrations of 8-OHdG in the CSF of AD patients (r(s) = 0.66, P < 0.001). The present study suggests that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of early AD development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry / physiology
  • DNA Damage / physiology*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / cerebrospinal fluid
  • Female
  • Free Radicals / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Diseases / cerebrospinal fluid*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / physiopathology
  • Nerve Degeneration / cerebrospinal fluid
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology
  • Oxidative Stress / physiology*
  • Ubiquinone / cerebrospinal fluid*

Substances

  • Biomarkers
  • Free Radicals
  • Ubiquinone
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine