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Open Access 01-12-2010 | Research article

ApoE mimetic peptide decreases Aβ production in vitro and in vivo

Authors: S Sakura Minami, Antoinette Cordova, John R Cirrito, Joseph A Tesoriero, Lenard W Babus, Gary C Davis, Sivanesan Dakshanamurthy, R Scott Turner, Daniel TS Pak, G William Rebeck, Mikell Paige, Hyang-Sook Hoe

Published in: Molecular Neurodegeneration | Issue 1/2010

Abstract

Background

Apolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ 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 Aβ 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 Aβ 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 Aβ 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 sAPPα and decreased Aβ levels at 24 hrs after treatment, suggesting that the apoE dimer may increase α-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 sAPPα and decreased Aβ levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Aβ production both in vitro and in vivo.

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Title: ApoE mimetic peptide decreases Aβ production in vitro and in vivo
Authors: S Sakura Minami
Antoinette Cordova
John R Cirrito
Joseph A Tesoriero
Lenard W Babus
Gary C Davis
Sivanesan Dakshanamurthy
R Scott Turner
Daniel TS Pak
G William Rebeck
Mikell Paige
Hyang-Sook Hoe
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2010
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-5-16

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Springer Medicine

ApoE mimetic peptide decreases Aβ production in vitro and in vivo

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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