TRANSFORMING GROWTH-FACTOR-BETA MEDIATES INCREASE OF MATURE TRANSMEMBRANE AMYLOID PRECURSOR PROTEIN IN MICROGLIAL CELLS

By using the immortalized microglial cell line BV-2, we show that the high expression of the beta A4 amyloid precursor protein (APP), its bi ogenesis and metabolism is modulated by TGF beta, a cytokine with immu nosuppressive activity, and by the microglia-stimulating agent LPS. TG F beta induces accumulation of cellular mature APP, the putative precu rsor of the amyloid subunit of Alzheimer's disease. LPS leads to an in crease in cellular immature, non-amyloidogenic APP and secretion of al so non-amyloidogenic APP fragments. We also demonstrate a functional i nvolvement of ECM molecules in the regulation of microglial APP expres sion at mRNA and protein level by TGF beta and LPS.