Characterization of 8‐Epiprostaglandin F 2α as aMarker of Amyloid β‐Peptide‐Induced Oxidative Damage

: The amyloid β‐peptide (Aβ) is a major componentof the neuritic plaques that are a defining histological characteristic ofAlzheimer's disease. Aβ can be directly toxic and pro‐inflammatory tocells in vitro. Numerous reports have shown that oxidative damage and reactiveoxygen species play a role in Aβ‐mediated neurotoxicity.8‐Epiprostaglandin F 2α (8‐isoprostane) is a well characterized product of lipid peroxidation that is formed nonenzymatically in cell membranes following an oxidative insult. We report a time‐ and concentration‐dependent increase in 8‐isoprostane levels in rat hippocampal cultures treated with Aβ(1‐40) or hydrogen peroxide. As evidence that 8‐isoprostane production is part of an Aβ toxic pathway, alkaline‐treated peptide, which shows minimal toxic activity, resulted in greatly attenuated 8‐isoprostane production. Although the increase in 8‐isoprostane levels preceded cell death, exogenously added 8‐isoprostane had no cytotoxic effects. The antioxidants vitamin E and propyl gallate attenuated Aβ‐induced 8‐isoprostane formation yet had no effect on Aβ‐induced lactate dehydrogenase release. Neither vitamin E nor propyl gallate had any effect on Aβ's ability to adopt a β‐pleated sheet structure and deposit on cells as determined by thioflavine S fluorescence. We conclude that 8‐isoprostane is an indicator of Aβ‐induced damage but not necessarily a mediator of Aβ‐induced neurotoxicity. Also, 8‐isoprostane could be a useful marker for assessing oxidative damage in the CNS.