Nonsteroidal anti-inflammatory drugs and Alzheimer's disease - Update on recent data and their therapeutic implications

A great number of immune and inflammatory markers have been found to be loc alised in the senile plaques that are hallmark lesions of Alzheimer's disea se. Complement proteins, cytokines, acute phase reactants, proteoglycans, p roteases and protease inhibitors, along with activated microglia and reacti ve astrocytes, have all been found to be closely associated with beta-amylo id deposits. Moreover, several epidemiological studies and a small pilot cl inical trial have reported a protective effect of prolonged anti-inflammato ry drug use against Alzheimer's disease. Among the anti-inflammatory compou nds, nonsteroidal anti-inflammatory drugs (NSAIDs) have been, the most exte nsively investigated agents in both basic scientific and epidemiological st udies. Although contradictory findings exist and some studies were affected by met hodological biases, the vast body of evidence supports the hypothesis of a direct contribution of the inflammatory response to the neurodegeneration a ssociated with Alzheimer's disease, and suggests that long term anti-inflam matory drug treatment might delay the onset or, at least, slow the progress ion of the disease. Present knowledge must be expanded to develop more specific, effective and well tolerated drugs, and controlled clinical trials are required to provid e conclusive evidence for a protective action of NSAIDs, or any other compo unds, in Alzheimer's disease.