Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease

This study showed increased thymine glycol, 4,6-diamino-5-formamidopyrimidine, FapyGua, and 5-hydroxyuracil, a degradation product of cytosine in various brain regions in Alzheimer’s disease

M. A. Lovell; W. R. Markesbery


Scholarcy highlights

  • Increasing evidence supports a role for oxidative DNA damage in aging and several neurodegenerative diseases including Alzheimer’s disease
  • AD subjects often present clinically with amnestic mild cognitive impairment, which is thought to be a transition between normal aging and early dementia and at present likely represents the best opportunity for pharmacologic interventions
  • It is interesting that levels of base adducts in MCI were not significantly different from those observed in late-stage AD subjects, suggesting oxidative damage to DNA in addition to other biomolecules is an early event in the pathogenesis of neuron degeneration in AD and may play a meaningful role in progression of the disease
  • The levels of 8-OHG, the predominant marker of DNA oxidation, in MCI are comparable to those observed in LAD, suggesting DNA oxidation occurs early in the progression of AD
  • The observation of increased mitochondrial DNA and nDNA oxidation in MCI, the earliest detectable phase of AD suggests that DNA damage is not a secondary event in the pathogenesis of AD but may contribute in a meaningful way to neurodegeneration observed in AD
  • The studies reviewed here suggest DNA oxidation and diminished repair capacities may play a role in the progression of AD, considerably more work is needed to clarify the mechanisms of DNA oxidation in the disease process

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