EVIDENCE AGAINST THE INVOLVEMENT OF REACTIVE OXYGEN SPECIES IN THE PATHOGENESIS OF NEURONAL DEATH IN DOWNS-SYNDROME AND ALZHEIMERS-DISEASE

It has been proposed that the pathogenesis of Down's Syndrome (DS) inv olves reactive oxygen species (ROS) arising from a gene dosage effect that disproportionately elevates superoxide dismutase (SOD1) activity. It was also suggested that generation of ROS might be responsible for neuronal death in Alzheimer's Disease (AD). Little data on brain ROS in DS and AD exist; therefore, we determined activities of choline ace tyltransferase (ChAT) and of the oxidative defense enzymes SOD1 and gl utathione peroxidase (GSHPx) in frontal cortex of aged patients with D S and AD. We also measured levels of malondialdehyde, which reflects l ipid peroxidation, and o-tyrosine, which represents the hydroxyl radic al attack. ChAT was significantly reduced in cortex of patients with D S (-68%) and AD (-66%) as compared to controls. There were no statisti cally significant differences, however, between controls and both neur odegenerative disorders for SOD1, GSHPx, malondialdehyde and o-tyrosin e. Our data contradict the only previous finding on increased SOD1 and ROS in brains of patients with DS: age as well as methodological diff erences might account for the discrepancy. In conclusion, no evidence for a pathogenetic role of SOD1, GSHPx, lipid peroxidation or hydroxyl radical attack in aged patients with DS and AD could be provided.