title: Reelin delays amyloid-beta fibril formation and rescues cognitive deficits in a model of Alzheimer's disease.
abstract: Reelin is an extracellular matrix protein that is crucial for neural development and adult brain plasticity. While the Reelin signalling cascade has been reported to be associated with Alzheimer's disease (AD), the role of Reelin in this pathology is not understood. Here we use an in vitro approach to show that Reelin interacts with amyloid-β (Aβ42) soluble species, delays Aβ42 fibril formation and is recruited into amyloid fibrils. Furthermore, Reelin protects against both the neuronal death and dendritic spine loss induced by Aβ42 oligomers. In mice carrying the APP(Swe/Ind) mutation (J20 mice), Reelin overexpression delays amyloid plaque formation and rescues the recognition memory deficits. Our results indicate that by interacting with Aβ42 soluble species, delaying Aβ plaque formation, protecting against neuronal death and dendritic spine loss and preventing AD cognitive deficits, the Reelin pathway deserves consideration as a therapeutic target for the treatment of AD pathogenesis.
authors.affiliation: 1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4] Vall D'Hebrón Institut de Recerca (VHIR), Barcelona 08035, Spain [5].
authors.forename: Lluís
authors.initials: L
authors.lastname: Pujadas
authors.affiliation: 1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4].
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.affiliation: 1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Andrés
authors.affiliation: 1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain.
authors.forename: Cátia M
authors.initials: CM
authors.lastname: Teixeira
authors.affiliation: Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Serra-Vidal
authors.affiliation: 1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4] CIEN Foundation, Madrid 28031, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Parcerisas
authors.affiliation: Department of Experimental Sciences and Health, University Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.affiliation: 1] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [2] Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.affiliation: Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Carulla
authors.affiliation: 1] Department of Cell Biology, University of Barcelona, Barcelona 08028, Spain [2] Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid 28031, Spain [3] Institute for Research in Biomedicine, Barcelona (IRB Barcelona), Barcelona 08028, Spain [4] Vall D'Hebrón Institut de Recerca (VHIR), Barcelona 08035, Spain [5] CIEN Foundation, Madrid 28031, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D049229:Dendritic Spines / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D011485:Protein Binding; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000091042:Reelin Protein; C075222:amyloid beta-protein (1-42); C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases