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

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العنوان: A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease ; Nat Commun
المؤلفون: TSARTSALIS, S., SLEVEN, H., FANCY, N., WESSELY, F., SMITH, A. M., WILLUMSEN, N., CHEUNG, T. K. D., ROKICKI, M. J., CHAU, V., IFIE, E., KHOZOIE, C., ANSORGE, O., YANG, X., JENKYNS, M. H., DAVEY, K., MCGARRY, A., MUIRHEAD, R. C. J., DEBETTE, Stephanie, JACKSON, J. S., MONTAGNE, A., OWEN, D. R., MINERS, J. S., LOVE, S., WEBBER, C., CADER, M. Z., MATTHEWS, P. M.
سنة النشر: 2024
مصطلحات موضوعية: Sciences du Vivant [q-bio]/Santé publique et épidémiologie
الوصف: Brain 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. ; EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking.
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 2041-1723
Relation: https://oskar-bordeaux.fr/handle/20.500.12278/201037
DOI: 10.1038/s41467-024-46630-z
الاتاحة: https://oskar-bordeaux.fr/handle/20.500.12278/201037
https://hdl.handle.net/20.500.12278/201037
https://doi.org/10.1038/s41467-024-46630-z
Rights: Attribution 3.0 United States ; open ; http://creativecommons.org/licenses/by/3.0/us/ ; Pas de Licence CC
رقم الانضمام: edsbas.89ABD206
قاعدة البيانات: BASE
الوصف
تدمد:20411723
DOI:10.1038/s41467-024-46630-z