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Neurobiol Dis. 2009 Jun;34(3):525-34. doi: 10.1016/j.nbd.2009.03.007. Epub 2009 Apr 1.

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

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Atherosclerosis Research Unit and Department of Medicine, University of Alabama at Birmingham Medical Center, Birmingham, AL-35294, USA.


Recent evidence indicates that inflammation may significantly contribute to the pathogenesis of Alzheimer's disease (AD). Since the apo A-I mimetic peptide D-4F has been shown to inhibit atherosclerotic lesion formation and regress already existing lesions (in the presence of pravastatin) and the peptide also decreases brain arteriole inflammation, we undertook a study to evaluate the efficacy of oral D-4F co-administered with pravastatin on cognitive function and amyloid beta (A beta) burden in the hippocampus of APPSwe-PS1 Delta E9 mice. 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 served as control. The escape latency in the Morris Water Maze test was significantly shorter for the D-4F+statin administered animals compared to the other two groups. While the hippocampal region of the brain was covered with 4.2+/-0.5 and 3.8+/-0.6% of A beta load in the control and ScD-4F+statin administered groups, in the D-4F+statin administered group A beta load was only 1.6+/-0.1%. Furthermore, there was a significant decrease in the number of activated microglia (p<0.05 vs the other two groups) and activated astrocytes (p<0.05 vs control) upon oral D-4F+statin treatment. Inflammatory markers TNFalpha and IL-1 beta levels were decreased significantly in the D-4F+statin group compared to the other two groups (for IL-1 beta p<0.01 vs the other two groups and for TNF-alpha p<0.001 vs control) and the expression of MCP-1 were also less in D-4F+statin administered group compared to the other two groups. These results suggest that the apo A-I mimetic peptide inhibits amyloid beta deposition and improves cognitive function via exerting anti-inflammatory properties in the brain.

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