Alzheimer's disease (AD) is a serious public health problem for the United States. Experimental, post mortem, and initial clinical trials all support the hypothesis that regionally increased brain lipid peroxidation may contribute to the pathogenesis of AD. Lacking, however, has been the means to objectively measure brain lipid peroxidation during life. The long-term objective of this project is to determine if isoprostanes and neuroprostanes, specific free radical-mediated products of arachidonic acid (AA) and docosahexaenoic acid (DHA) peroxidation, respectively are quantitative intra vitam biomarkers of brain lipid peroxidation that may serve as surrogate biomarkers for AD severity, progression, and response to anti-oxidant interventions.
The specific aims for this project are: 1) to determine if isoprostanes and neuroprostanes are accurate intra vitam biomarkers of brain lipid peroxidation, 2) to determine if the extent of brain lipid peroxidation, quantified by isoprostanes and neuroprostanes, correlates with AD severity and progression, and 3) to determine effective concentrations and doses of anti-oxidants that suppress brain isoprostane and neuroprostane production, and 3) to determine effective concentrations and doses of anti-oxidants that suppress brain isoprostane and neuroprostane production in vitro and in vivo. This new information will establish the relationship between brain lipid peroxidation and the progression of AD, and guide future development of anti-oxidant therapy for patients with AD.
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