Amyloid-beta aggregates induce vasculopathy via ferroptosis in brain endothelial cells

Recent studies have demonstrated the dysfunction of the blood-brain barrier (BBB) in AD; however, how Aβ plaque induces BBB dysfunction, particularly in brain endothelial cells (ECs), remains elusive. This study investigates the lipid peroxidation-mediated ferroptosis pathway induced by Aβ by conducting RNA sequencing, phosphorylation analysis, metabolite analysis, western blotting, and immunofluorescent staining both in vitro and in vivo.

Here, we found that Aβ is associated with lipid metabolic pathways following Aβ exposure in brain ECs. Additionally, Aβ aggregates induce the formation and accumulation of peroxidized lipid droplets. Lastly, Aβ is significantly reduced in brain ECs and 5xFAD mice by the inhibition of the lipid metabolic pathway associated with lipid peroxidation and ROS formation.