Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides

Apolipoprotein E plays an important role in recovery from acute brain injur y and risk of developing AZzheimer's disease. We demonstrate that biologica lly relevant concentrations of apoE suppress microglial activation and rele ase of TNF alpha and NO in a dose-dependent fashion. Peptides derived from the apoE receptor-binding region mimic the effects of the intact protein, w hereas deletion of apoE residues 146-149 abolishes peptide bioactivity. The se results are consistent with the hypothesis that apoE modulates microglia l function by binding specific cell surface receptors and that the immunomo dulatory effects of apoE in the central nervous system may account for its role in acute and chronic neurological disease. (C) 2001 Academic Press.