Endothelial DR6 in blood-brain barrier malfunction in Alzheimer's disease.

ABSTRACT: The impairment of the blood-brain barrier (BBB) has been increasingly recognised as a critical element in the early pathogenesis of Alzheimer's disease (AD), prompting a focus on brain endothelial cells (BECs), which serve as the primary constituents of the BBB. Death receptor 6 (DR6) is highly expressed in brain vasculature and acts downstream of the Wnt/β-catenin pathway to promote BBB formation during development. Here, we found that brain endothelial DR6 levels were significantly reduced in a murine model of AD (APP_swe/PS1_dE9 mice) at the onset of amyloid-β (Aβ) accumulation. Toxic Aβ_25-35 oligomer treatment recapitulated the reduced DR6 in cultured BECs. We further showed that suppressing DR6 resulted in BBB malfunction in the presence of Aβ_25-35<

SUBMITTER: Huang X 

PROVIDER: S-EPMC11014957 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature