Microglial Phagocytosis and AB-Mediated Neurotoxicity

Project Summary

Microglia are specialized phagocytic cells of the central nervous system that engulf or phagocytize material and also mediate inflammatory responses. Based on these properties, they are thought to play a role in AD, especially since cell culture studies have shown that they can also phagocytize Ab. However, there is also some evidence that microglia do not effectively break down internalized Ab. This may lead to chronic activation and contribute to the progression of the disease. Dr. Webster is trying to determine whether the ingestion of Ab by brain cells causes the release of neurotoxic inflammatory molecules called cytokines. The production of oxygen-free radicals is also being monitored, and the production of both cytokines and free radicals will be correlated with the amount of undegraded Ab present inside the microglial cells. This information is important because some of the therapies currently being explored, such as an Ab vaccine, are predicated on the assumption that increased uptake of Ab by microglia will alleviate disease. However, if Ab activates microglia inflammatory responses, then the strategy of stimulating uptake could actually worsen the disease.