In vivo and in vitro effects of an apolipoprotein e mimetic peptide on amyloid-β pathology.

Academic Article

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.
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    Keywords

  • Amyloid Neuropathies, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Antipsychotic Agents, Apolipoproteins E, Brain, Cell Line, Transformed, Cholesterol, Cognition Disorders, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Hippocampus, Humans, Lipoproteins, Male, Maze Learning, Mice, Mice, Transgenic, Mutation, Peptide Fragments, Plaque, Amyloid, Presenilin-1, Transfection
  • Digital Object Identifier (doi)

    Authorlist

  • Handattu SP; Monroe CE; Nayyar G; Palgunachari MN; Kadish I; van Groen T; Anantharamaiah GM; Garber DW
  • Start Page

  • 335
  • End Page

  • 347
  • Volume

  • 36
  • Issue

  • 2