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

Patrizia Mecocci MD, Usha MacGarvey MS, Dr. M. Flint Beal MD. Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Correspondence to M. Flint Beal, Neurochemistry Laboratory, Warren 408, Massachusetts General Hospital, Boston, MA 02114

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 (OH 8 dG), in DNA isolated from three regions of cerebral cortex and cerebellum in 1 3 AD and 1 3 age-matched controls. There was a significant threefold increase in the amount of OH 8 dG 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.