ASTROCYTES REGULATE MICROGLIAL PHAGOCYTOSIS OF SENILE PLAQUE CORES OFALZHEIMERS-DISEASE

We have developed an in vitro model in which isolated senile plaque (S P) cores are presented to rat microglial cells in culture. Microglia r apidly phagocytosed, broke apart, and cleared SP cores. However, when cocultured with astrocytes, microglial phagocytosis was markedly suppr essed, allowing the SPs to persist. Suppression of phagocytosis by ast rocytes appears to be a general phenomena since microglia in the prese nce of astrocytes showed reduced capacity to phagocytose latex beads a s well. The astrocyte effect on microglia is related in part to a diff usible factor(s) since astrocyte-but not fibroblast-conditioned media also reduced phagocytosis. These results suggest that while microglia have the capacity to phagocytose and remove SPs, astrocytes which lie in close association to microglia may help prevent the efficient clear ance of SP material allowing them to persist in Alzheimer's disease. ( C) 1998 Academic Press.