HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin

HIV-1-infected brains are characterized by increased amyloid deposition. To study the influence of HIV-1 on amyloid beta (A beta) homeostasis at the blood-brain barrier (BBB) level, we employed a model of brain microvascular endothelial cells exposed to HIV-1 in the presence or absence of A beta. HIV-1 markedly increased endogenous A beta levels and elevated accumulation of exogenous A beta. Simvastatin, the HMG-CoA reductase inhibitor, blocked these effects. We next evaluated the effects of HIV-1 and/or simvastatin on expression of the receptor for lipoprotein related protein (LRP1) and the receptor for advanced glycation end products (RAGE), known to regulate A beta transport across the BBB. LRP1 expression was not affected by HIV-1; however, it was increased by simvastatin. Importantly, simvastatin attenuated HIV-1-induced RAGE expression. These results suggest that HIV-1 may directly contribute to A beta accumulation at the BBB level. In addition, statins may protect against increased A levels associated with HIV-1 infection in the brain. (C) 2009 Elsevier Inc. All rights reserved.