Stergios Tsartsalis, Hannah Sleven, Nurun Fancy, Frank Wessely, Amy M Smith, Nanet Willumsen, To Ka Dorcas Cheung, Michal J Rokicki, Vicky Chau, Eseoghene Ifie, Combiz Khozoie, Olaf Ansorge, Xin Yang, Marion H Jenkyns, Karen Davey, Aisling McGarry, Robert C J Muirhead, Stephanie Debette, Johanna S Jackson, Axel Montagne, David R Owen, J Scott Miners, Seth Love, Caleb Webber, M Zameel Cader, Paul M Matthews
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 β-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...
March 12, 2024: Nature Communications