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

TLDR

Oxidative damage to DNA may contribute to normal aging and neurodegenerative diseases. The study examined whether Alzheimer’s disease is associated with increased oxidative damage to nuclear and mitochondrial DNA in postmortem brain tissue. The authors quantified 8‑hydroxy‑2′‑deoxyguanosine in DNA from three cortical regions and cerebellum of 13 AD patients and 13 age‑matched controls. They found a three‑fold increase in mitochondrial DNA oxidation in parietal cortex and, overall, a small rise in nuclear DNA oxidation but a highly significant three‑fold rise in mitochondrial DNA oxidation in AD versus controls, confirming that mtDNA is especially vulnerable and may contribute to neurodegeneration.

Abstract

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 (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.