Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice

Lara Ordóñez-Gutiérrez, Francesca Re, Erika Bereczki, Eniko Ioja, Maria Gregori, Alina J. Andersen, Marta Antón, S. Moein Moghimi, Jin Jing Pei, Massimo Masserini, Francisco Wandosell

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid or cardiolipin over 3. weeks. This treatment reduced significantly the amount of Aβ in the plasma and the brain levels of Aβ were lighter affected. Nevertheless, this dosing regimen did modulate tau phosphorylation and glycogen synthase kinase 3 activities in the brain, suggesting that the targeting of circulating Aβ may be therapeutically relevant in AD.

Original languageEnglish (US)
Pages (from-to)421-430
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • APP/PS1
  • Alzheimer treatment
  • Amyloid-β
  • Nanoparticles

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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