Simvastatin Therapy Prevents Brain Trauma-Induced Increases in β-Amyloid Peptide Levels

Elevations in beta-amyloid peptide (A beta) levels after traumatic brain injury (TBI) may confer risk for developing Alzheimer's disease in head trauma patients. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on hippocampal A beta burden in a clinically relevant head injury/intervention model using mice expressing human A beta. Simvastatin therapy blunted TBI-induced increases in A beta, reduced hippocampal tissue damage and microglial activation, and improved behavioral outcome. The ability of statins to reduce post-injury A beta load and ameliorate pathological sequelae of brain injury makes them potentially effective in reducing the risk of developing Alzheimer's disease in TBI patients.