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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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dc.contributor.authorOikari, L.E.
dc.contributor.authorPandit, R.
dc.contributor.authorStewart, R.
dc.contributor.authorCuní-López, C.
dc.contributor.authorQuek, H.
dc.contributor.authorSutharsan, R.
dc.contributor.authorRantanen, L.M.
dc.contributor.authorOksanen, M.
dc.contributor.authorLehtonen, S.
dc.contributor.authorde Boer, C.M.
dc.contributor.authorPolo, J.M.
dc.contributor.authorGötz, J.
dc.contributor.authorKoistinaho, J.
dc.contributor.authorWhite, A.R.
dc.date.issued2020
dc.description.abstractThe 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.
dc.description.statementofresponsibilityLotta E.Oikari, Rucha Pandit, Romal Stewart, Carla Cuní-López, Hazel Quek, Ratneswary Sutharsan .. et al.
dc.identifier.citationStem Cell Reports, 2020; 14(5):924-939
dc.identifier.doi10.1016/j.stemcr.2020.03.011
dc.identifier.issn2213-6711
dc.identifier.issn2213-6711
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133432
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1118452
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1125796
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1145580
dc.rights© 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/
dc.source.urihttps://doi.org/10.1016/j.stemcr.2020.03.011
dc.subjectBlood-Brain Barrier
dc.subjectCells, Cultured
dc.subjectCell Line
dc.subjectEndothelial Cells
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectAlzheimer Disease
dc.subjectDextrans
dc.subjectConnexins
dc.subjectUltrasonic Therapy
dc.subjectCapillary Permeability
dc.subjectPhenotype
dc.subjectPresenilin-1
dc.subjectInduced Pluripotent Stem Cells
dc.subjectAmyloid beta-Peptides
dc.subject.meshBlood-Brain Barrier
dc.subject.meshCells, Cultured
dc.subject.meshCell Line
dc.subject.meshEndothelial Cells
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshAlzheimer Disease
dc.subject.meshDextrans
dc.subject.meshConnexins
dc.subject.meshUltrasonic Therapy
dc.subject.meshCapillary Permeability
dc.subject.meshPhenotype
dc.subject.meshPresenilin-1
dc.subject.meshInduced Pluripotent Stem Cells
dc.subject.meshAmyloid beta-Peptides
dc.titleAltered brain endothelial cell phenotype from a familial Alzheimer mutation and its potential implications for amyloid clearance and drug delivery
dc.typeJournal article
pubs.publication-statusPublished

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