Apolipoprotein E receptors mediate the effects of beta-amyloid on astrocyte cultures

We have previously shown that beta -amyloid (A beta) induces astrocyte acti vation in vitro and that this reaction is attenuated by the addition of exo genous apolipoprotein E (apoE)-containing particles. However, the effects o f A beta on endogenous apoE and apoJ levels and the potential role of apoE receptors in astrocyte activation have not been addressed. Three activating stimuli (lipopolysaccharide, dibutyryl cAMP, and aged A beta 1-42) were us ed to induce activation of rat astrocyte cultures, as assessed by changes i n morphology and an increase in interleubin-1 beta. However, only A beta al so induced similar to 50% reduction in the amount of released apoE and apoJ and an 8-fold increase in the levels of cell-associated apoE and apoJ, Exp eriments using two concentrations of receptor-associated protein, an inhibi tor of apoE receptors with a differential affinity for the low density lipo protein receptor (LDLR) and the LDLR-related protein (LRP), suggest that LR P mediates A beta -induced astrocyte activation, whereas LDLR mediates the A beta -induced changes in apoE levels. Receptor-associated protein had no effect on apoJ levels or on activation by either dibutyryl cAMP or lipopoly saccharide. These data suggest that apoE receptors translate the presence o f extracellular A beta into cellular responses, both initiating and modulat ing the inflammatory response induced by A beta.