BETA-AMYLOID PEPTIDE SECRETION BY A MICROGLIAL CELL-LINE IS INDUCED BY BETA-AMYLOID-(25-35) AND LIPOPOLYSACCHARIDE

beta-Amyloid protein (beta AP) deposition is a neuropathologic hallmar k of Alzheimer's disease (AD). Yet, the source of cerebral beta AP in AD is controversial. We examined the production of beta AP by the BV-2 immortalized microglial cell Line using a sensitive enzyme immunoassa y. Constitutive production of beta AP was detected in conditioned medi a from unstimulated BV-2 cells. Further, production of beta AP was ind uced by treatment of cultures by lipopolysaccharide (LPS) or beta AP-( 25-35) and was inhibited by the calpain protease inhibitor MDL 28170. Treatment of BV-2 cells with LPS or beta AP-(25-35) did not affect cel l-associated beta-amyloid precursor protein levels. These findings sug gest that microglia may be an important source of beta AP in AD, and t hat microglial production of beta AP may be augmented by proinflammato ry stimuli or by beta AP itself.