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Simvastatin therapy prevents brain trauma-induced increases in beta-amyloid peptide levels


Year of Publication:
Contact PI Name:
Steven T. DeKosky
Contact PI Affiliation:
Department of Neurology, Brain Trauma Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Eric E. Abrahamson, Milos D. Ikonomovic, C. Edward Dixon
Primary Reference (PubMED ID):
Funding Source:
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

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

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
HMG-CoA Reductase

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported
Animal Model Notes:
TgAPPSwe-KI mice producing the highest amounts of human Aβ were designated APPNLh/APPNLh.

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Morris Water Maze
Hidden Platform Task
Motor Function
Balance Beam Test
Cortical and Hippocampal Tissue Loss
Activated Microglia
Synaptic Density
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42