title: Repeated intraperitoneal injections of liposomes containing phosphatidic acid and cardiolipin reduce amyloid-β levels in APP/PS1 transgenic mice.
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 3weeks. 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.
  
  
  BACKGROUND
  Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected - although to a lesser extent - suggesting that targeting of circulating Aß may be therapeutically relevant of Alzheimer's disease.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), C/ Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain; Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), C/ Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Ordóñez-Gutiérrez
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza, MB, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
authors.affiliation: Karolinska Institutet, KI-Alzheimer Disease Research Center, Novum, Huddinge, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.affiliation: Karolinska Institutet, KI-Alzheimer Disease Research Center, Novum, Huddinge, Sweden.
authors.forename: Eniko
authors.initials: E
authors.lastname: Ioja
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza, MB, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Gregori
authors.affiliation: Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark.
authors.forename: Alina J
authors.initials: AJ
authors.lastname: Andersen
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), C/ Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain; Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), C/ Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Antón
authors.affiliation: Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark; NanoScience Centre, Faculty of Science, University of Copenhagen, Copenhagen Ø, Denmark.
authors.forename: S Moein
authors.initials: SM
authors.lastname: Moghimi
authors.affiliation: Karolinska Institutet, KI-Alzheimer Disease Research Center, Novum, Huddinge, Sweden.
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Pei
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza, MB, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Masserini
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), C/ Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain; Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), C/ Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain. Electronic address: fwandosell@cbm.uam.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Wandosell
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002308:Cardiolipins / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010712:Phosphatidic Acids / Q000008:administration & dosage* / Q000737:chemistry; D016875:tau Proteins / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002308:Cardiolipins; D008081:Liposomes; D010712:Phosphatidic Acids; D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3
keywords: APP/PS1; Alzheimer treatment; Amyloid-β; Nanoparticles