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Oxidatively modified RNA in mild cognitive impairment

Mark A Lovell1, William R Markesbery

  • 1Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA. malove2@uky.edu

Neurobiology of Disease
|October 9, 2007
PubMed

Insights

Oxidative damage, specifically RNA oxidation, is elevated in the brains of individuals with mild cognitive impairment (MCI) and Alzheimer

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Oxidative damage is a known hallmark of Alzheimer's disease (AD) and mild cognitive impairment (MCI).
  • The specific role of RNA oxidation in the early stages of neurodegeneration, such as MCI, remains largely unexplored.

Purpose of the Study:

  • To investigate the presence and significance of RNA oxidation in the hippocampus/parahippocampal gyrus (HPG) of subjects with MCI.
  • To compare RNA oxidation levels in MCI with those in late-stage AD (LAD) and age-matched normal controls (NC).

Main Methods:

  • Immunohistochemistry was performed on HPG sections from MCI, LAD, and NC subjects using antibodies for 8-hydroxyguanine (8-OHG) and 1-N2-propanodeoxyguanosine (NPrG).
  • Confocal microscopy was used to quantify immunostaining.
  • RNase and DNase-I treatments were employed to determine the association of adducts with RNA or DNA.

Main Results:

  • Significantly elevated levels of 8-OHG and NPrG immunostaining were observed in the HPG of MCI and LAD subjects compared to NC subjects (p<0.05).
  • The observed adducts were predominantly localized to neurons exhibiting early tau alterations (MC-1 antibody positive).
  • Enzymatic pretreatment indicated that the adducts were primarily associated with RNA, and RNA oxidation levels in MCI were comparable to LAD.

Conclusions:

  • RNA oxidation is significantly increased in mild cognitive impairment and is associated with early neurodegenerative changes in tau.
  • These findings suggest that RNA oxidation is an early event in the pathogenesis of neuronal degeneration in Alzheimer's disease.

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