THE INFLAMMATORY RESPONSE SYSTEM OF BRAIN - IMPLICATIONS FOR THERAPY OF ALZHEIMER AND OTHER NEURODEGENERATIVE DISEASES

Cultured brain cells are capable of generating many molecules associat ed with inflammatory and immune functions. They constitute the endogen ous immune response system of brain. They include complement proteins and their regulators, inflammatory cytokines, acute phase reactants an d many proteases and protease inhibitors. Most of the proteins are mad e by microglia and astrocytes, but even neurons are producers. Many ap pear in association with Alzheimer disease lesions, indicating a state of chronic inflammation in Alzheimer disease brain. Such a state can apparently exist without stimulation by peripheral inflammatory mediat ors or the peripheral immune system. A strong inflammatory response ma y be autotoxic to neurons, exacerbating the fundamental pathology in A lzheimer disease and perhaps other neurological disorders. Autotoxic p rocesses may contribute to cellular death in chronic inflammatory dise ases affecting other parts of the body, suggesting the general therape utic value of anti-inflammatory agents. With respect to Alzheimer dise ase, multiple epidemiological studies indicate that patients taking an ti-inflammatory drugs or suffering from conditions in which such drugs are routinely used, have a decreased risk of developing Alzheimer dis ease. In one very preliminary clinical trial, the anti-inflammatory dr ug indomethacin arrested progress of the disease. New agents directed against the inflammatory processes revealed in studies of Alzheimer di sease lesions may have broad therapeutic applications.