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.

• Authors: Shaila P Handattu, Candyce E Monroe, Gaurav Nayyar, Mayakonda N Palgunachari, Inga Kadish, Thomas van Groen, G M Anantharamaiah, David W Garber
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 36 Issue 2 Pg. 335-47 ( 2013) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 23603398 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ac-hE18A-NH(2)
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Antipsychotic Agents
• Apolipoproteins E
• Lipoproteins
• PSEN1 protein, human
• Peptide Fragments
• Presenilin-1
• amyloid beta-protein (1-42)
• Cholesterol

Topics

• Amyloid Neuropathies (complications, drug therapy, metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Antipsychotic Agents (therapeutic use)
• Apolipoproteins E (metabolism)
• Brain (drug effects, metabolism)
• Cell Line, Transformed
• Cholesterol (blood)
• Cognition Disorders (drug therapy, etiology, genetics)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Hippocampus (drug effects, metabolism, pathology)
• Humans
• Lipoproteins (therapeutic use)
• Male
• Maze Learning (drug effects)
• Mice
• Mice, Transgenic
• Mutation (genetics)
• Peptide Fragments (metabolism, therapeutic use)
• Plaque, Amyloid (drug therapy, etiology, genetics)
• Presenilin-1 (genetics)
• Transfection