Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain

The epsilon 4 allele of the apolipoprotein E gene (APOE) is associated with sporadic and familial late-onset Alzheimer's disease (AD). Oxidative stres s is believed to play an important role in neuronal dysfunction and cell de ath in AD. We now provide evidence that in the hippocampus of AD, the level of thiobarbituric acid-reactive substances (TBARS) and the APOE genotype a re linked. Within AD cases, the levels of TBARS were found to be higher amo ng epsilon 4 carriers while the apoE protein concentrations were lower. The relationship between the levels of TBARS and apoE proteins was corroborate d by the results from the APOE-deficient mice, in which the levels of TBARS were higher than those in wild-type mice. Among AD cases, tissues from pat ients with the E4 allele of APOE displayed lower activities of catalase and glutathione peroxidase and lower concentration of glutathione than tissues from patients homozygous for the epsilon 3 allele of APOE. Together these data demonstrate that, in AD, the epsilon 4 allele of APOE is associated wi th higher oxidative insults. (C) 2000 Academic Press.