Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease

Abstract

Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. We examined whether Alzheimer's disease (AD) is associated with increased oxidative damage to both nDNA and mtDNA in postmortem brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2′-deoxyguanosine (OH⁸dG), in DNA isolated from three regions of cerebral cortex and cerebellum in 13 AD and 13 age-matched controls. There was a significant threefold increase in the amount of OH⁸dG in mtDNA in parietal cortex of AD patients compared with controls. In the entire group of samples there was a small significant increase in oxidative damage to nDNA and a highly significant threefold increase in oxidative damage to mtDNA in AD compared with age-matched controls. These results confirm that mitochondrial DNA is particularly sensitive to oxidative damage, and they show that there is increased oxidative damage to DNA in AD, which may contribute to the neurodegenerative process.