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Postmortem studies have associated Alzheimer's disease (AD) with regionally increased oxidative damage to brain. Lacking, however, is a specific marker of oxidative damage to brain that may be measured during life. We tested the hypothesis that cerebrospinal fluid (CSF) concentrations of F2-isoprostanes (F2-IsoPs), stable products of arachidonate peroxidation, are increased in CSF of AD patients. CSF from lateral ventricles (VF) was analyzed from 11 AD patients and 11 control subjects who participated in a rapid autopsy program. VF F2-IsoP concentrations were significantly elevated in AD patients compared with control subjects (72 +/- 7 vs 46 +/- 4 pg/ml) and were significantly linearly correlated with brain weight (-0.3 pg/ml/g, r2 = 0.32). These results suggest that quantification of CSF F2-IsoP concentrations may provide a useful biomarker of central nervous system oxidative damage in AD.