IMMUNE-MECHANISMS IN NEURODEGENERATIVE DISORDERS

Recent immunohistochemical and molecular biological studies, particula rly in Alzheimer's disease (AD) but also in other chronic neurological disorders, have suggested the brain is capable of an innate inflammat ory responsse characterized by the appearance of activated microglia a nd complement proteins, including the membrane attack complex which is capable of bystander lysis of healthy neurons. There is also the appe arance or upregulation of inflammatory cytokines, acute phase reactant s, and many proteases and protease inhibitors. Most of the proteins ar e made by microglia and astrocytes, but even neurons are producers. Th is chronic inflammatory response in brain can apparently occur without stimulation by peripheral inflammatory mediators or involvement of th e peripheral immune system. Its existence in AD brain has led to the h ypothesis that antiinflammatory drugs might stop progression of the di sease or inhibit its onset. Seventeen epidemiological studies generall y support this hypothesis. Moreover, in one small clinical trial the a ntiinflammatory drug indomethacin was found to arrest progression of t he mental deterioration over the 6 months of the trial. Slowing the pr ogress of early AD or inhibiting its onset would have enormous pharmac oeconomic as well as human benefits. Further clinical trials in AD and other chronic neurological disorders seem warranted.