EXPRESSION OF THE ALZHEIMER AMYLOID-PROMOTING FACTOR ANTICHYMOTRYPSINIS INDUCED IN HUMAN ASTROCYTES BY IL-1

The amyloid deposits of Alzheimer's disease contain, in addition to th e beta protein (Ap), lesser amounts of other proteins including the pr otease inhibitor alpha-antichymotrypsin (ACT). We have recently shown that ACT acts as a pathological chaperone, binding to the beta protein and strongly promoting its polymerization into amyloid filaments in v itro. The data of this paper show that ACT synthesis is induced in cul tured human astrocytes by IL-1, a lymphokine whose expression is stron gly up-regulated in microglial cells in affected areas of Alzheimer's disease brain. Furthermore, unfractionated glial cultures containing b oth astrocytes and microglia from human cortex (which develops amyloid in Alzheimer's disease) spontaneously express IL-1 and ACT as they re ach confluence. In contrast, confluent mixed glial cultures similarly prepared from human cerebellum or brain stem, or from rat brain tissue s not prone to amyloid formation-do not express ACT unless supplemente d with exogenous IL-1. The same regional difference in IL-1 expression by microglia is seen in vivo in Alzheimer's disease. These results in dicate that the IL-1-induced expression of ACT may help direct the reg ion-specific production of mature amyloid filaments in the Alzheimer b rain.