Angiopoietin signalling is a central axis of amyloid-driven vascular dysfunction in Alzheimer's disease.

ABSTRACT: The neurovascular unit is critical for brain health, and its dysfunction has been linked to Alzheimer's disease (AD). However, a cell-type-resolved understanding of how diverse vascular cells become dysfunctional and contribute to disease has been missing. Here, we applied Vessel Isolation and Nuclei Extraction for Sequencing (VINE-seq) to build a comprehensive transcriptomic atlas from 101 individuals along AD progression. Our analysis of over 842,646 parenchymal and vascular nuclei reveals that vascular dysfunction in AD is driven by transcriptional changes rather than shifts in cell proportions, with brain endothelial cells (BECs) and smooth muscle cells (SMCs) most affected. Strikingly, these molecular signatures emerge early at the mild cognitive impairment (MCI) stage, implicating va

SUBMITTER: Flotho M 

PROVIDER: S-EPMC12407677 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature