AMYLOID-BETA PROTEIN (A-BETA) REMOVAL BY NEUROGLIAL CELLS IN CULTURE

Because the mechanisms of A beta degradation in normal and Alzheimer's disease brain are poorly understood, we have examined whether various cortical cells are capable of processing this peptide. Rat microglia and astrocytes, as well as the human THP-1 monocyte cell line, degrade d A beta(1-42) added to culture medium. In contrast, neither rat corti cal neurons or meningeal fibroblasts effectively catabolized this pept ide. When A beta fibrils were immobilized as plaque-like deposits on c ulture dishes, both microglia and THP-1 cells removed the peptide. Ast rocytes were incapable of processing the A beta deposits, but these ce lls released glycosaminoglycase-sensitive molecules that inhibited the subsequent removal of A beta by microglia. This implied that astrocyt e-derived proteoglycans associated with the amyloid peptide and slowed its degradation. The addition of purified proteoglycan to A beta that was in medium or focally deposited also resulted in significant inhib ition of peptide removal by microglia. These data suggest that A beta can be catabolized by microglia and proteoglycans which co-localize wi th senile plaques may slow the degradation of A beta within these path ologic bodies.