Cited by 63Alzheimer's disease research and treatmentsBarrier Structure and Function StudiesDrug Transport and Resistance Mechanisms

Modulation of Amyloid-β1–40 Transport by ApoA1 and ApoJ Across an in vitro Model of the Blood-Brain Barrier

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Merino-Zamorano, Cristina, Fernández-de Retana, Sofía, Montañola, Alex, Batlle, Aina, Saint-Pol, Julien, Mysiorek, Caroline, Gosselet, Fabien, Montaner, Joan +1 more·2016·Journal of Alzheimer's Disease

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.

Integrity signals

Registry

Crossref · 10.3233/jad-150976

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  • Trans-BBB efflux of Aβ into peripheral blood circulation is one of the main pathways of physiological clearance, with ApoE, ApoJ, and ApoA1 as chaperones.

    “Several groups have reported that trans-BBB efflux of Aβ into peripheral blood circulation is one of the main pathways of physiological clearance with ApoE, ApoJ, and ApoA1 as chaperones27,31,32.”

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Authors
Merino-Zamorano, C., Fernández-de Retana, S., Montañola, A., Batlle, A., Saint-Pol, J., Mysiorek, C., Gosselet, F., Montaner, J., & Hernández-Guillamon, M.
Affiliations
  • Universitat Autònoma de Barcelona (ES)
  • Neurovascular Research Laboratory, Vall d’Hebron Research Insitute, Universitat Autònoma de Barcelona, Barcelona, Spain
  • Univ. Artois, EA2465, Laboratoire de la Barrière Hémato-Encéphalique, LBHE, Lens, F-62300, France
  • Université d'Artois (FR)
Venue
Journal of Alzheimer's Disease
Published
2016-07-13
Volume
53
Issue
2
Pages
677-691
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
OpenAlex
W2394652749
Cited by
63
References
61
Citations by year
2026: 2 · 2025: 5 · 2024: 12 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 3 · 2017: 5 · 2016: 2
FWCI
5.11
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
amyloid-β1-40, blood-brain barrier
MeSH terms
Animals, Biological Transport, Blood-Brain Barrier, Capillary Permeability, Cell Line, Transformed, Cerebral Cortex, Humans, Mice, Inbred C57BL, Peptide Fragments, RNA, Messenger, Transfection, Amyloid beta-Peptides, Apolipoprotein A-I, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial Cells, Immunoprecipitation, Clusterin, Mice, HEK293 Cells, Zonula Occludens-1 Protein

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