Oxidatively modified nucleic acids in preclinical Alzheimer's disease (PCAD) brain

Mark A. Lovell, Sony Soman, Melissa A. Bradley

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


Previous studies show increased oxidative DNA and RNA damage and diminished 8-oxoguanine glycosylase (OGG1) mediated base excision repair in vulnerable brain regions of mild cognitive impairment and late-stage Alzheimer's disease (LAD) subjects compared to normal control (NC) subjects. Recently, a preclinical stage of AD (PCAD) has been described in which subjects show no overt clinical manifestations of AD but demonstrate significant AD pathology at autopsy. To determine if DNA or RNA oxidation are significantly elevated in PCAD brain we quantified 8-hydroxyguanine (8-OHG) in sections of hippocampus/parahippocamapal gyri in PCAD and NC subjects using immunohistochemistry and confocal microscopy and in superior and middle temporal gyri (SMTG) using gas chromatography/mass spectrometry. To determine if increased DNA oxidation is associated with altered repair capacity, levels of OGG1 protein in HPG were measured by immunohistochemistry and levels of OGG1 mRNA were measured in SMTG using quantitative PCR. Results show significantly increased (p<0.05) 8-OHG immunostaining in DNA and RNA of PCAD HPG and significantly increased 8-OHG in PCAD SMTG. Quantification of OGG1 showed significantly elevated mRNA in PCAD SMTG and a trend toward elevated protein immunostaining in PCAD HPG. Overall, the data suggest oxidative damage to nucleic acids and a compensatory increase in OGG1 expression occur early in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)443-448
Number of pages6
JournalMechanisms of Ageing and Development
Issue number8-9
StatePublished - Aug 2011

Bibliographical note

Funding Information:
This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank the UK-ADC Clinical, Neuropathology and Biostatistics Cores for tissue procurement, neuropathologic and neuropsychological data. The authors also thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.


  • Base excision repair
  • DNA oxidation
  • Oxidative stress
  • Preclinical AD
  • RNA oxidation

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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