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 β (Aβ) burden in the hippocampus of APPSwe-PS1ΔE9 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 Aβ load in the control and ScD-4F + statin administered groups, in the D-4F + statin administered group Aβ 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 TNFα and IL-1β levels were decreased significantly in the D-4F + statin group compared to the other two groups (for IL-1β p < 0.01 vs the other two groups and for TNF-α 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 β deposition and improves cognitive function via exerting anti-inflammatory properties in the brain.
|Original language||English (US)|
|Number of pages||10|
|Journal||Neurobiology of Disease|
|State||Published - Jun 2009|
Bibliographical noteFunding Information:
This work was supported in part by Institute for the Study of Aging (S.P.H), NHLBI PO1 HL 34343 (D.W.G) and NIA AG 031846 (L.L). The behavioral studies were performed at Behavioral Assessment core, Dept. of Neurobiology, UAB which is supported by P30 NS47466.
- A-I mimetic
- Amphipathic peptides
- Amyloid β
- Apo A-I