Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders.

Alzheimer and a number of other neurodegenerative diseases are characterized by the presence of reactive microglia and reactive astrocytes in association with the lesions. The classic view that microglia exist primarily in either a resting or activated state needs to be broadened in view of recent results. Resting microglia are in constant activity sampling their surround. Activated microglia may be pro-inflammatory, releasing inflammatory cytokines and other inflammatory mediators, or anti-inflammatory, promoting the healing process. There is evidence that microglial phagocytosis is more powerful in the anti-inflammatory state. Activated astrocytes also have pro-inflammatory and anti-inflammatory properties. In the pro-inflammatory state they release inflammatory cytokines. In the anti-inflammatory state they release various growth factors. In AD and other neurodegenerative diseases, both microglia and astrocytes are in a pro-inflammatory state. From a therapeutic point of view it is desirable to find methods of tipping the balance towards an anti-inflammatory state for both types of glia.