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Increased free radical-mediated injury to brain is proposed to be an integral component of several neurodegenerative diseases, including Alzheimer's disease (AD). Lipid peroxidation is a major outcome of free radical- mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. F₂-Isoprostanes (F₂-IsoPs), one group of lipid peroxidation products derived from arachidonic acid, are especially useful as in vivo biomarkers of lipid peroxidation. F₂-IsoP concentration is selectively increased in diseased regions of brain from patients who died from advanced AD, where pathologic changes include amyloid β (Aβ) amyloidogenesis, neurofibrillary tangle formation, and extensive neuron death. Interestingly, cerebral F₂-IsoPs are not reproducibly elevated in aged mouse models of cerebral Aβ amyloidogenesis only. There is broad agreement that increased cerebrospinal fluid (CSF) levels of F₂-IsoPs also are present in patients with early AD. Demonstrated applications of quantifying CSF F₂-IsoPs have improved laboratory diagnostic accuracy of AD and objective assessment of antioxidant therapeutics. In contrast, quantification of F₂-IsoPs in plasma and urine of AD patients has produced conflicting data. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F₂-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD. Antioxid. Redox Signal. 7, 269–275.