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Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease


Year of Publication:
Contact PI Name:
Shaila Handattu
Contact PI Affiliation:
Atherosclerosis Research Unit and Department of Medicine, University of Alabama at Birmingham Medical Center, Birmingham, Alabama, USA
David W. Garber, Candyce E. Monroe, Thomas van Groen, Inga Kadish, Gaurav Nayyar, Dongfeng Cao, Mayakonda N. Palgunachari, Ling Li, G.M. Anantharamaiah
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Institute for the Study of Aging (ISOA)
National Heart Lung and Blood Institute (NHLBI)
Study Goal and Principal Findings:

Apolipoprotein A-I (apo A-I) is the major protein component of HDL; it possess several important protective properties/functions  including modulation of cholesterol transport and thereby development of atherosclerosis and, anti-inflammatory and anti-oxidant properties. In the presence of pravastatin the apo A-I mimetic peptide D-4F has been shown to inhibit atherosclerotic lesion formation and regress already existing lesions. In this study the authors tested the hypothesis that oral administration of the apo A-I mimetic peptide, D-4F, co-administered with pravastatin (at a dose at which this statin alone does not inhibit Aβ deposition), would decrease Aβ deposition in the brain and improve cognitive performance in APPswe-PS1ΔE9 transgenic mouse model of AD. Three groups of male mice were administered D-4F and pravastatin, Scrambled D-4F (ScD-4F, a control peptide) and pravastatin in drinking water, while drinking water alone. Results showed that, in the presence of pravastatin, the peptide D-4F, but not the control scrambled peptide ScD-4F, significantly inhibits Aβ deposition and improves cognitive performance.  In addition, D-4F and pravastatin treatment was associated with decreased numbers of activated microglia and reactive astrocytes in the hippocampal region and a concomitant decrease in pro-inflammatory cytokine levels in the brain. These results, along with a large number of previous investigations, support the idea that anti-inflammatory apo A-I mimetics may also be a potential drug for AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Peptide
Therapeutic Agent:
D-4F Mimetic Peptide
Therapeutic Target:
Multi Target
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
HMG-CoA Reductase

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
(C57BL/6 x C3H)F2

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
beta Amyloid Load
Activated Microglia
Activated Astrocytes
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Amyloid Precursor Protein (APP)
Amyloid Precursor Protein (APP) Metabolites
Tumor Necrosis Factor alpha (TNF alpha)
Interleukin 1 beta (IL-1 beta)
Chemokine C-C Motif Ligand 2/Monocyte Chemoattractant Protein 1 (CCL2/MCP1)