Fatty Acid Oxidation in the Pathogenesis of Alzheimer's Disease

Alzheimer's disease (AD) is the most common dementing illness of the elderly and is a mounting public health problem. Pharmacoepidemiological data, analytical data from human tissue and body fluids, and mechanistic data mostly from murine models all have implicated oxidation products of two fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), in the pathogenesis of neurodegeneration. Here we review the biochemistry of AA and DHA oxidation, both enzyme-catalyzed and free radical mediated, and summarize those studies that have investigated these oxidation products as effectors of neurodegeneration and biomarkers of AD. Given the evolving appreciation for toxicity associated with current pharmaceuticals used to block AA and DHA oxidation, we close by speculating on likely areas of future research directed at suppressing this facet of neurodegeneration. If successful, these interventions are unlikely to cure AD, but may check its explosive growth and hopefully reduce its incidence and prevalence in the elderly.