Evidence against the involvement of reactive oxygen species in the pathogenesis of neuronal death in Down's syndrome and Alzheimer's disease.
It has been proposed that the pathogenesis of Down's Syndrome (DS) involves 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 acetyltransferase (ChAT) and of the oxidative defense enzymes SOD1 and glutathione peroxidase (GSHPx) in frontal cortex of aged patients with DS and AD. We also measured levels of malondialdehyde, which reflects lipid peroxidation, and o-tyrosine, which represents the hydroxyl radical attack. ChAT was significantly reduced in cortex of patients with DS (-68%) and AD (-66%) as compared to controls. There were no statistically significant differences, however, between controls and both neurodegenerative disorders for SOD1, GSHPx, malondialdehyde and o-tyrosine. Our data contradict the only previous finding on increased SOD1 and ROS in brains of patients with DS: age as well as methodological differences 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.
Hayn
M
M
Department of Biochemistry, University of Graz, Austria.
Kremser
K
K
Singewald
N
N
Cairns
N
N
Nemethova
M
M
Lubec
B
B
Lubec
G
G
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D016923:Cell Death; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism
D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase