Postmortem studies have associated Alzheimer's disease (AD) with regio
nally increased oxidative damage to brain. Lacking, however, is a spec
ific marker of oxidative damage to brain that may be measured during l
ife. We tested the hypothesis that cerebrospinal fluid (CSF) concentra
tions of F-2-isoprostanes (F-2-IsoPs), stable products of arachidonate
peroxidation, are increased in CSF of AD patients. CSF from lateral v
entricles (VF) was analyzed from 11 AD patients and 11 control subject
s who participated in a rapid autopsy program. VF F-2-IsoP concentrati
ons were significantly elevated in AD patients compared with control s
ubjects (72 +/- 7 vs 46 +/- 4 pg/ml) and were significantly linearly c
orrelated with brain weight (-0.3 pg/ml/g, r(2) = 0.32). These results
suggest that quantification of CSF F-2-IsoP concentrations may provid
e a useful biomarker of central nervous system oxidative damage in AD.