Nonsteroidal antiinflammatory drugs as therapeutic agents for Alzheimer's disease

One feature of the end-stage pathology of Alzheimer's disease (AD) is the presence of numerous inflammatory markers associated with the amyloid beta protein (Abeta) deposits in the brain. Experimental data strongly suggests that Abeta aggregates can incite an inflammatory response, but there are also data suggesting that inflammation can promote Abeta production and deposition. Thus, anti inflammatory drugs may have some role in AD therapy. This idea is supported by epidemiologic data, which shows that long-term use of nonsteroidal anti inflammatory drugs (NSAIDs) confers protection from the development of AD. Significantly, oral salicylates have not been consistently shown to confer protection. Such studies have raised questions regarding the target or targets of NSAIDs that account for their apparent protection from AD. We have recently found that some NSAIDs have a novel mechanism of action, namely, selective lowering of the pathogenic Abeta42 peptide, that could contribute to their efficacy in AD. Further study will be needed to determine if the classic anti inflammatory properties of NSAIDs, the Abeta42-lowering property, another known or unknown property, or a combination of these contributes to NSAIDs apparent ability to protect individuals from the development of AD.