Evidence against increased oxidative DNA-damage in Down syndrome

In Down syndrome (DS), oxidative DNA-damage may play a role in the pathogenesis of characteristic mental retardation and precocious dementia of Alzheimer type. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (8-OHdG), in nuclear DNA (nDNA) isolated from four different regions of cerebral cortex and cerebellum in 10 adult DS and 10 Alzheimer's disease (AD) patients compared to normal controls. Levels of 8-OHdG in post-mortem brain tissue were investigated by means of high-performance liquid chromatography with electrochemical detection. There was no significant increase in DS and AD compared to controls in any of the brain regions. Highest amounts of 8-OHdG were in temporal cortex in DS (180.0 +/- 9.6 nmol/g wet weight tissue), AD (172.4 +/- 14.6 nmol/g wet weight tissue) and controls (183.4 +/- 12.7 nmol/g). We conclude that the results provide evidence against an increased reactive oxygen species (ROS) induced damage to nDNA in DS and AD.