Remarkable increase in the concentration of 8-hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer's disease

J Neurosci Res. 2002 Nov 1;70(3):447-50. doi: 10.1002/jnr.10349.

Abstract

To investigate the possible role of oxidative RNA damage in the pathogenesis of Alzheimer's disease (AD), the concentrations of the oxidative stress marker 8-hydroxyguanosine (8-OHG) were measured in the cerebrospinal fluid (CSF) and the serum of patients with AD and control subjects. The concentration of 8-OHG in CSF in AD patients was approximately fivefold that in controls (P < 0.001). The concentration of 8-OHG in CSF decreased significantly with the duration of illness (r(s) = -0.48, P < 0.05) and the progression of cognitive dysfunctions (r(s) = 0.67, P < 0.01). However, the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and AD patients. In addition, the concentration of 8-OHG in serum was not significantly altered in AD patients compared to that in controls, suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue. These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics
  • Brain / metabolism
  • Brain / physiopathology
  • Female
  • Guanosine / analogs & derivatives*
  • Guanosine / blood
  • Guanosine / cerebrospinal fluid*
  • Humans
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Oxidative Stress / genetics*
  • RNA / metabolism*
  • Up-Regulation / genetics*

Substances

  • Guanosine
  • 8-hydroxyguanosine
  • RNA