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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.
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https://hal-univ-artois.archives-ouvertes.fr/hal-02506917
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Submitted on : Thursday, March 12, 2020 - 4:04:24 PM
Last modification on : Wednesday, March 25, 2020 - 3:43:18 PM

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Cristina Merino-Zamorano, Sofía Fernández-de Retana, Alex Montañola, Aina Batlle, Julien Saint-Pol, et al.. Modulation of Amyloid-β1–40 Transport by ApoA1 and ApoJ Across an in vitro Model of the Blood-Brain Barrier. Journal of Alzheimer's Disease, IOS Press, 2016, 53 (2), pp.677-691. ⟨10.3233/JAD-150976⟩. ⟨hal-02506917⟩

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