Differential alterations in antioxidant capacity in cells from Alzheimer patients

Oxidative stress occurs in brains of Alzheimer's disease (AD) patients. A m ajor question in AD research is whether the oxidative stress is just second ary to neurodegeneration. To test whether oxidative stress is an inherent p roperty of AD tissues, the ability of cultured fibroblasts bearing the AD P resenilin-1 246 Ala --> Glu mutation to handle reactive oxygen species (ROS ) was compared to controls. Although ROS in cells from AD subjects were onl y slightly less than cells from controls under basal conditions (-10%) or a fter exposure to H2O2 (-16%), treatment with antioxidants revealed clear di fferences. Pretreatment with DMSO, a hydroxyl radical scavenger, reduced ba sal and H2O2-induced ROS levels significantly more in cells from controls ( -22%, -22%) than in those from AD subjects (-4%, + 14%). On the other hand, pretreatment with Trolox diminished Zi,O-2-induced ROS significantly more in cells from AD (-60%) than control subjects (-39%). In summary, cells fro m AD patients have greater Trolox sensitive ROS and less DMSO sensitive ROS than controls. The results demonstrate that fibroblasts bearing this PS-1 mutation have altered means of handling oxidative stress and appear useful for determining the mechanism underlying the altered redox metabolism. (C) 2000 Elsevier Science B.V. All rights reserved.