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A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease

dc.rights.licenseopenen_US
dc.contributor.authorTSARTSALIS, S.
dc.contributor.authorSLEVEN, H.
dc.contributor.authorFANCY, N.
dc.contributor.authorWESSELY, F.
dc.contributor.authorSMITH, A. M.
dc.contributor.authorWILLUMSEN, N.
dc.contributor.authorCHEUNG, T. K. D.
dc.contributor.authorROKICKI, M. J.
dc.contributor.authorCHAU, V.
dc.contributor.authorIFIE, E.
dc.contributor.authorKHOZOIE, C.
dc.contributor.authorANSORGE, O.
dc.contributor.authorYANG, X.
dc.contributor.authorJENKYNS, M. H.
dc.contributor.authorDAVEY, K.
dc.contributor.authorMCGARRY, A.
dc.contributor.authorMUIRHEAD, R. C. J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorJACKSON, J. S.
dc.contributor.authorMONTAGNE, A.
dc.contributor.authorOWEN, D. R.
dc.contributor.authorMINERS, J. S.
dc.contributor.authorLOVE, S.
dc.contributor.authorWEBBER, C.
dc.contributor.authorCADER, M. Z.
dc.contributor.authorMATTHEWS, P. M.
dc.date.accessioned2024-07-19T12:48:06Z
dc.date.available2024-07-19T12:48:06Z
dc.date.issued2024-03-12
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/201037
dc.description.abstractEnBrain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased beta-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD. Vascular pathology may play important early role in Alzheimer's disease (AD). Here, the authors show that beta-amyloid induces transcriptomic signatures associated with accelerated apoptosis, impaired function and AD risk in human brain microvasculature.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enA single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease
dc.title.alternativeNat Communen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41467-024-46630-zen_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38472200en_US
dc.description.sponsorshipEuropeEU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking.en_US
bordeaux.journalNature Communicationsen_US
bordeaux.page2243en_US
bordeaux.volume15en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04654261
hal.version1
hal.date.transferred2024-07-19T12:48:11Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Communications&rft.date=2024-03-12&rft.volume=15&rft.issue=1&rft.spage=2243&rft.epage=2243&rft.eissn=2041-1723&rft.issn=2041-1723&rft.au=TSARTSALIS,%20S.&SLEVEN,%20H.&FANCY,%20N.&WESSELY,%20F.&SMITH,%20A.%20M.&rft.genre=article


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