Immunosuppression Could Attenuate Tau Pathology
The concept based on the premise that anti-inflammatory therapy may prevent or retard the development of AD originated with the discovery that neuroinflammation strongly correlates with AD and that it is associated with senile plaque pathology and NFTs. Moreover, epidemiological studies have indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) lower the risk of developing AD. In accord with these findings, several drugs, such as the nonselective or COX2-selective NSAIDs and glucocorticoid steroids, were studied to determine if they offer any benefits to AD patients. However, randomized controlled trials assessing COX2 inhibitors (rofecoxib and celecoxib), COX1 and COX2 inhibitors (naproxen and indomethacin) and glucocorticoids (prednisone) failed to demonstrate any beneficial effect on cognition, behaviour or activities of daily living among AD patients. Furthermore, NSAIDs were not associated with reductions in the load of neuritic plaques (NPs) or NFTs in human AD brain. On the contrary, one study showed that heavy NSAID use was associated with a significant increase in NPs. In contrast, it has been shown that the use of corticosteroids significantly decreased the density of NPs and NFTs in the entorhinal cortices, hippocampi and amygdalae of AD patients. Similarly, immunosuppressive treatment of young transgenic mice expressing mutant tau P301S attenuated tau pathology and increased lifespan. This animal study revealed that targeted inhibition of the inflammatory response can reduce tau pathology and ameliorate disease progression.