The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease

Abstract

Genetic evidence suggests that generation of amyloid beta peptide is the pivotal step in the pathophysiology of Alzheimer's disease (AD). The mechanism by which this peptide induces neurodegeneration may involve inflammatory processes. Pharmacological suppression of inflammation may therefore ameliorate the neuropathology. Basic research studies provide substantial evidence that inflammatory processes present in the brains of patients with AD are destructive, and that anti-inflammatory drugs can provide protection. Furthermore, epidemiological studies suggest that anti-inflammatory drugs reduce the risk of AD. However, there is not yet any strong evidence from completed randomised controlled trials that anti-inflammatory treatment is beneficial. Large trials of glucocorticoid therapy, hydroxychloroquine, and non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of AD have so far been disappointing. Several studies, including a large primary prevention trial with NSAIDs, are still in progress. Major issues of selection of patients, drug regimen, and duration of treatment remain unresolved.