Bibliographic
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.