title: ApoE mimetic peptide decreases Abeta production in vitro and in vivo.
abstract: BACKGROUND
  Apolipoprotein E (apoE) is postulated to affect brain Abeta levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Abeta degradation, and Abeta clearance. We previously showed that an apoE-derived peptide containing a double repeat of the receptor-binding region was similarly effective in increasing APP processing in vivo. Here, we further examined whether peptides containing tandem repeats of the apoE receptor-binding region (amino acids 141-149) affected APP trafficking, APP processing, and Abeta production.
  
  
  RESULTS
  We found that peptides containing a double or triple tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased cell surface APP and decreased Abeta levels in PS1-overexpressing PS70 cells and in primary neurons. This effect was potentiated by a sequential increase in the number of apoE receptor-binding domain repeats (trimer > dimer > monomer). We previously showed that the apoE dimer increased APP CTF in vivo; to determine whether the dimer also affected secreted APP or Abeta levels, we performed a single hippocampal injection of the apoE dimer in wild-type mice and analyzed its effect on APP processing. We found increased sAPPalpha and decreased Abeta levels at 24 hrs after treatment, suggesting that the apoE dimer may increase alpha-secretase cleavage.
  
  
  CONCLUSIONS
  These data suggest that small peptides consisting of tandem repeats of the apoE receptor-binding region are sufficient to alter APP trafficking and processing. The potency of these peptides increased with increasing repeats of the receptor binding domain of apoE. In addition, in vivo administration of the apoE peptide (dimer) increased sAPPalpha and decreased Abeta levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Abeta production both in vitro and in vivo.
authors.affiliation: Department of Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. map65@georgetown.edu.
authors.forename: S Sakura
authors.initials: SS
authors.lastname: Minami
authors.forename: Antoinette
authors.initials: A
authors.lastname: Cordova
authors.forename: John R
authors.initials: JR
authors.lastname: Cirrito
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tesoriero
authors.forename: Lenard W
authors.initials: LW
authors.lastname: Babus
authors.forename: Gary C
authors.initials: GC
authors.lastname: Davis
authors.forename: Sivanesan
authors.initials: S
authors.lastname: Dakshanamurthy
authors.forename: R Scott
authors.initials: RS
authors.lastname: Turner
authors.forename: Daniel Ts
authors.initials: DTs
authors.lastname: Pak
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
authors.forename: Mikell
authors.initials: M
authors.lastname: Paige
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
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