The isoprostane 8,12-iso-iPF2alpha-VI is a sensitive and specific marker of in vivo lipid peroxidation. We found elevated levels in the urine, blood, and cerebrospinal fluid of patients with Alzheimer's disease (AD) that correlated with measures of cognitive and functional impairment, established biomarkers of AD pathology (cerebrospinal fluid tau and amyloid) and the number of apolipoprotein E epsilon4 alleles. These results suggest that 8,12-iso-iPF2alpha-VI is a useful biomarker of oxidative damage in AD.