title: The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles: Potential therapeutic approach for Alzheimer disease.
abstract: We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood-brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the 'brain' side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the 'blood' compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease. From the Clinical Editor: Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease.
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza MB, Italy. Electronic address: s.mancini6@campus.unimib.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Mancini
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza MB, Italy. Electronic address: stefania.minniti1@libero.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Minniti
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza MB, Italy. Electronic address: maria.gregori@unimib.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Gregori
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza MB, Italy. Electronic address: giulio.sancini@unimib.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Sancini
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. Electronic address: alfredo.cagnotto@marionegri.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France. Electronic address: pierre-olivier.couraud@inserm.fr.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Centro de Biologia MoLecular Severo Ochoa (CSIC-UAM) C/Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain. Electronic address: lordoniez@cbm.csic.es.
authors.forename: Lara
authors.initials: L
authors.lastname: Ordóñez-Gutiérrez
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Centro de Biologia MoLecular Severo Ochoa (CSIC-UAM) C/Nicolás Cabrera 1, Universidad Autónoma Madrid, Madrid, Spain. Electronic address: fwandosell@cbm.csic.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Wandosell
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. Electronic address: mario.salmona@marionegri.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Department of Health Sciences, University of Milano-Bicocca, Monza MB, Italy. Electronic address: francesca.re1@unimib.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Re
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000302:isolation & purification* / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D005240:Feasibility Studies; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer disease; Liposomes; Nanoparticles; Sink effect; β-Amyloid oligomers