In Vivo and In Vitro Effects of an Apolipoprotein E Mimetic Peptide on Amyloid-β Pathology

Abstract

Background:

Apolipoprotein E (ApoE) is the major apolipoprotein present in the high-density lipoprotein-like particles in the central nervous system (CNS). ApoE is involved in various protective functions in CNS including cholesterol transport, anti-inflammatory, and antioxidant effects. An ApoE peptide would be expected to exert protective effects on neuroinflammation.

Objective:

To determine the effects of an ApoE mimetic peptide Ac-hE18A-NH₂ on amyloid-β pathology.

Method:

Using human APP/PS1ΔE9 transgenic mice and in vitro studies, we have evaluated the effect of an ApoE mimetic peptide, Ac-hE18A-NH₂, on amyloid plaque deposition and inflammation.

Results:

Administration of Ac-hE18A-NH₂ to APP/PS1ΔE9 mice for 6 weeks (50 µg/mouse, 3 times a week) significantly improved cognition with a concomitant decrease in amyloid plaque deposition and reduced activated microglia and astrocytes, and increased brain ApoE levels. Oligomeric Aβ₄₂ (oAβ₄₂) and oxidized PAPC (ox-PAPC) inhibited secretion of ApoE in U251 cells, a human astrocyte cell line, and this effect was ameliorated in the presence of peptide Ac-hE18A-NH₂. The peptide also increased Aβ₄₂ uptake in a cell line of human macrophages.

Conclusions:

Peptide Ac-hE18A-NH₂ attenuates the effects of oxidative stress on ApoE secretion, inhibits amyloid plaque deposition, and thus could be beneficial in the treatment of Alzheimer’s disease.