DNA oxidation in Alzheimer's disease

William R. Markesbery, Mark A. Lovell

Research output: Contribution to journalReview articlepeer-review

124 Scopus citations

Abstract

Oxidative damage to DNA may play an important role in aging and neurodegenerative diseases such as Alzheimer's disease (AD). Attack on DNA by reactive oxygen species, particularly hydroxyl radicals, can lead to strand breaks, DNA-DNA and DNA-protein cross-linking, sister chromatid exchange and translocation, and formation of at least 20 oxidized base adducts. Modification of DNA bases can lead to mutation and altered protein synthesis. In late-stage AD brain, several studies have shown an elevation of the base adducts 8 hydroxyguanine (8-OHG), 8-hydroxyadenine (8-OHA), 5-hydroxycytosine (5-OHC), and 5-hydroxyuracil, a chemical degradation product of cytosine. Several studies have shown a decline in repair of 8-OHG in AD. Most recently, our studies have shown elevated 8-OHG, 8-OHA, and 5,6-diamino-5-formamidopyrimidine in nuclear and mitochondrial DNA in mild cognitive impairment, the earliest detectable form of AD, suggesting that oxidative damage to DNA is an early event in AD and not a secondary phenomenon.

Original languageEnglish
Pages (from-to)2039-2045
Number of pages7
JournalAntioxidants and Redox Signaling
Volume8
Issue number11-12
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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