title: Modulation of Amyloid-β1-40 Transport by ApoA1 and ApoJ Across an in vitro Model of the Blood-Brain Barrier.
abstract: Amyloid-β (Aβ) accumulation in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) is likely caused by the impairment of its brain clearance that partly occurs through the blood-brain barrier (BBB). In this context, an in vitro BBB model is a valuable tool for studying the molecular mechanisms that regulate this process. This study assessed brain Aβ elimination across the BBB and its modulation by the natural chaperones Apolipoprotein A1 (ApoA1) and Apolipoprotein J/Clusterin (ApoJ). The model was based on primary cerebral endothelial cells that were cultured on Matrigel-coated Transwells and treated with fluorescently labeled-Aβ1-40 to track its efflux across the BBB, which corresponds to trafficking from the basolateral (brain) to apical (blood) compartments. We observed that the transport of basolateral Aβ1-40 was enhanced when it was complexed to rApoJ, whereas the complex formed with rApoA1 did not influence Aβ1-40 efflux. However, the presence of rApoA1 in the apical compartment was able to mobilize Aβ1-40 from the basolateral side. We also observed that both rApoA1 and rApoJ moderately crossed the monolayer (from blood to brain) through a mechanism involving the LDL receptor-related protein family. In contrast to the increased rApoJ efflux when complexed to Aβ1-40, rApoA1 trafficking was restricted when it was bound to the Aβ peptide. In summary, the present study highlights the role of ApoJ and ApoA1 in the in vitro modulation of Aβ elimination across the BBB.
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Merino-Zamorano
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Fernández-de Retana
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Montañola
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Aina
authors.initials: A
authors.lastname: Batlle
authors.affiliation: Univ. Artois, EA2465, Laboratoire de la Barrière Hémato-Encéphalique, LBHE, Lens, F-62300, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Saint-Pol
authors.affiliation: Univ. Artois, EA2465, Laboratoire de la Barrière Hémato-Encéphalique, LBHE, Lens, F-62300, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mysiorek
authors.affiliation: Univ. Artois, EA2465, Laboratoire de la Barrière Hémato-Encéphalique, LBHE, Lens, F-62300, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Neurology, Neurovascular Unit, Vall d'Hebron Hospital, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.affiliation: Neurovascular Research Laboratory, Vall d'Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Hernández-Guillamon
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002540:Cerebral Cortex / Q000166:cytology; D051152:Clusterin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; C495242:CLU protein, human; D051152:Clusterin; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C078592:amyloid beta-protein (1-40)
keywords: Amyloid-beta; ApoA1; ApoJ; apolipoprotein; blood-brain barrier; endothelial cells