title: 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.
  
  
  METHODS
  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.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA. hande@uab.edu
authors.forename: Shaila P
authors.initials: SP
authors.lastname: Handattu
authors.forename: Candyce E
authors.initials: CE
authors.lastname: Monroe
authors.forename: Gaurav
authors.initials: G
authors.lastname: Nayyar
authors.forename: Mayakonda N
authors.initials: MN
authors.lastname: Palgunachari
authors.forename: Inga
authors.initials: I
authors.lastname: Kadish
authors.forename: Thomas
authors.initials: T
authors.lastname: van Groen
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
authors.forename: David W
authors.initials: DW
authors.lastname: Garber
mesh_terms: D017772:Amyloid Neuropathies / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D002784:Cholesterol / Q000097:blood; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008074:Lipoproteins / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism / Q000627:therapeutic use*; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D014162:Transfection
chemical_list: C478448:Ac-hE18A-NH(2); D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D001057:Apolipoproteins E; D008074:Lipoproteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D002784:Cholesterol