Modulation of Amyloid-β1–40 Transport by ApoA1 and ApoJ Across an in vitro Model of the Blood-Brain Barrier
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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.
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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.”
From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [31]
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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
- Publisher
- SAGE Publications
- 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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