Oxidatively modified RNA in mild cognitive impairment

Mark A. Lovell, William R. Markesbery

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Studies show increased oxidative damage in the brains of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). To determine if RNA oxidation occurs in MCI, sections of hippocampus/parahippocampal gyrus (HPG) from 5 MCI, 5 late stage AD (LAD) and 5 age-matched normal control (NC) subjects were subjected to immunohistochemistry using antibodies against 8-hydroxyguanine (8-OHG) and 1-N2-propanodeoxyguanosine (NPrG). Confocal microscopy showed 8-OHG and NPrG immunostaining was significantly (p < 0.05) elevated in MCI and LAD HPG compared with NC subjects and was predominately associated with neurons identified using the MC-1 antibody that recognizes conformational alterations of tau, which are associated with early neurofibrillary tangle formation. Pretreating sections with RNase or DNase-I showed immunostaining for both adducts was primarily associated with RNA. In addition, levels of both adducts in MCI were comparable to those measured in LAD, suggesting RNA oxidation may be an early event in the pathogenesis of neuron degeneration in AD.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalNeurobiology of Disease
Volume29
Issue number2
DOIs
StatePublished - Feb 2008

Bibliographical note

Funding Information:
Supported by NIH grants 5-P01-AG05119 and 1P30-AG028383, and by a grant from the Abercrombie Foundation. The authors thank Ms. Paula Thomason for technical and editorial assistance, and Ms. Sonya Anderson for subject demographic data.

Keywords

  • Alzheimer's disease
  • Lipid peroxidation
  • Mild cognitive impairment
  • Oxidative stress
  • RNA

ASJC Scopus subject areas

  • Neurology

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