Cyclooxygenase as a target for the antiamyloidogenic activities of nonsteroidal anti-inflammatory drugs in Alzheimer's disease

A large number of epidemiological studies have addressed the possible protective effect of anti-inflammatory drug use with regard to Alzheimer's disease (AD). The most convincing of these studies--the Baltimore Longitudinal Study of Aging--utilized data collected prospectively, thereby minimizing recall bias issues. However, despite this evidence, therapeutic studies investigating nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-1 (COX-1) and COX-2 inhibitors and steroids, do not support this hypothesis. This discrepancy may be due to the fact that the bulk of epidemiological evidence has examined the likely incidence of AD prior to the onset of clinical symptoms of disease. On the basis of this information, the article will attempt to formulate a possible scenario, in which optimal NSAIDs might be tested in the most favorable clinical therapeutic conditions in order to determine whether NSAIDs can provide beneficial treatment for the clinical progression of AD dementia.