Fellowships Grants and Awards August 2003 Toxicogenomics

Background: Inflammation and oxidative stress are both involved in the pathogenesis of Alzheimer disease and have been shown to be reciprocally linked. One group of molecules that have been directly associated with inflammation and the production of free radicals are the prostaglandin 13,14-dihydro 15-keto PGF2α and the isoprostane 8-iso-PGF2α. Results: To further delineate the role of inflammatory and oxidative parameters in Alzheimer disease, in this study we evaluated the amount and localization of 13,14-dihydro 15-keto PGF2α and 8-iso-PGF2α in hippocampal post mortem tissue samples from age-matched Alzheimer disease and control patients. Our results demonstrate increased levels of 13,14-dihydro 15-keto PGF2α and 8iso-PGF2α in the hippocampal pyramidal neurons of Alzheimer disease patients when compared to control patients. Conclusion: These data not only support the shared mechanistic involvement of free radical damage and inflammation in Alzheimer disease, but also indicate that multiple pathogenic "hits" are likely necessary for both the development and propagation of Alzheimer disease. Background Alzheimer disease (AD) is the leading cause of senile dementia, with a prevalence that is directly related to age [1]. Over 4 million individuals are currently affected with the disease in the United States alone and this number is projected to increase to 14 million by 2050 [2]. At the present time, therapeutic management of the disease is primarily focused on palliative treatment of the symptoms rather than forestalling the progression of the disease [3] and the major obstacle in designing a rationale for therapeutic targets is our incomplete understanding of pathogenesis. To this end, it is imperative that the mechanistic hallmarks of this disease are established. The tight association between aging and AD has led the field to propose oxidative stress as a major mechanism responsible for the onset and progression of AD [4]. Physiologically, the production of reactive oxygen species (ROS) is found in all aerobic organisms and arises from the secondary production of superoxide, hydrogen peroxPublished: 22 January 2007 Molecular Neurodegeneration 2007, 2:2 doi:10.1186/1750-1326-2-2 Received: 09 November 2006 Accepted: 22 January 2007 This article is available from: http://www.molecularneurodegeneration.com/content/2/1/2 © 2007 Casadesus et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.