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Simvastatin enhances learning and memory independent of amyloid load in mice


Year of Publication:
Contact PI Name:
Ling Li
Contact PI Affiliation:
Atherosclerosis Research Unit, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
Dongfeng Cao, Helen Kim, Robin Lester, Ken-ichiro Fukuchi
Primary Reference (PubMED ID):
Funding Source:
American Federation for Aging Research
Alzheimer's Association
National Institute on Aging (NIA)
American Heart Association
Study Goal and Principal Findings:

The overall aim of this investigation was to study the effects of a commonly used statin , simvastatin, on learning and memory in the Tg 2576  transgenic mouse model of AD, and non transgenic littermates. Simvastatin reduced plasma lipoprotein cholesterol levels with out hepatic toxicity. Simvastatin treatment not only reversed learning and memory deficits in the Tg2576 mice, but also enhanced learning and memory in the nontransgenic mice. However, Simvastatin treatment had no significant effect on the steady-state levels and depositions of β-amyloid in the brain of Tg mice. Simvastatin treatment did not affect the steady-state levels of cholesterol and apolipoprotein E in brain.   Simvastatin treatment was associated with increased expression levels of signal transduction pathways e.g.,  protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS), in mouse brain. In conclusion, this study showed that simvastatin treatment reversed learning and memory deficits in Tg2576 mice independent of cerebral Aβ levels and enhanced cognitive function in normal-aged non-Tg mice, and suggest that simvastatin may exert its beneficial effects directly through modulation of signaling pathways in memory formation independent CNS beta amyloid levels.

Therapeutic Agent

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

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

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
T Maze
Morris Water Maze
Elevated Plus Maze
Open Field Test
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Apolipoprotein E (ApoE)
phospho-Protein Kinase B (phospho-Akt/PKB)
Endothelial Nitric Oxide Synthase (eNOS/NOS3)
High-Density Lipoprotein Cholesterol (HDL-C)
Plasma-Total Cholesterol
Target Engagement (Reduction Total Cholesterol-Plasma)
Food Intake
Body Weight