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  • Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery

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    Author(s)
    Oikari, Lotta E
    Pandit, Rucha
    Stewart, Romal
    Cuni-Lopez, Carla
    Quek, Hazel
    Sutharsan, Ratneswary
    Rantanen, Laura M
    Oksanen, Minna
    Lehtonen, Sarka
    de Boer, Carmela Maria
    Polo, Jose M
    Goetz, Juergen
    Koistinaho, Jari
    White, Anthony R
    Griffith University Author(s)
    Sutharsan, Ratneswary
    Year published
    2020
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    Abstract
    The blood-brain barrier (BBB) presents a barrier for circulating factors, but simultaneously challenges drug delivery. How the BBB is altered in Alzheimer disease (AD) is not fully understood. To facilitate this analysis, we derived brain endothelial cells (iBECs) from human induced pluripotent stem cells (hiPSCs) of several patients carrying the familial AD PSEN1 mutation. We demonstrate that, compared with isogenic PSEN1 corrected and control iBECs, AD-iBECs exhibit altered tight and adherens junction protein expression as well as efflux properties. Furthermore, by applying focused ultrasound (FUS) that transiently opens ...
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    The blood-brain barrier (BBB) presents a barrier for circulating factors, but simultaneously challenges drug delivery. How the BBB is altered in Alzheimer disease (AD) is not fully understood. To facilitate this analysis, we derived brain endothelial cells (iBECs) from human induced pluripotent stem cells (hiPSCs) of several patients carrying the familial AD PSEN1 mutation. We demonstrate that, compared with isogenic PSEN1 corrected and control iBECs, AD-iBECs exhibit altered tight and adherens junction protein expression as well as efflux properties. Furthermore, by applying focused ultrasound (FUS) that transiently opens the BBB and achieves multiple therapeutic effects in AD mouse models, we found an altered permeability to 3–5 kDa dextran as a model cargo and the amyloid-β (Aβ) peptide in AD-iBECs compared with control iBECs. This presents human-derived in vitro models of the BBB as a valuable tool to understand its role and properties in a disease context, with possible implications for drug delivery.
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    Journal Title
    Stem Cell Reports
    Volume
    14
    Issue
    5
    DOI
    https://doi.org/10.1016/j.stemcr.2020.03.011
    Copyright Statement
    © 2020 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Biological Sciences
    Biochemistry and Cell Biology
    Clinical Sciences
    Science & Technology
    Life Sciences & Biomedicine
    Cell & Tissue Engineering
    BLOOD-BRAIN
    Publication URI
    http://hdl.handle.net/10072/397755
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    • Journal articles

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