Influence of Alzheimer’s associated Aβ oligomers and oxidative stress on blood–brain barrier dysfunction

Abstract

Blood–brain barrier (BBB) dysfunction is an early event observed in Alzheimer’s disease (AD). Two characteristics of AD brain and brain vasculature contribute to BBB dysfunction: the accumulation of aggregated amyloid-β protein (Aβ) and an increase in oxidative stress. This work uses a BBB model of primary human brain microvascular endothelial cells to investigate the individual and synergistic influence of both pathogenic Aβ oligomers and oxidative stress on BBB transendothelial electrical resistance (TEER), an indicator of barrier integrity. Results indicate that nontoxic, physiological concentrations of Aβ oligomers reduce TEER, while Aβ monomer remains inert. Moreover, introducing mild oxidative stress, which alone does not influence monolayer integrity, exacerbates the effect of Aβ oligomers on TEER within this BBB model. These findings advance the understanding of BBB dysfunction in AD and point toward therapeutic strategies targeting this early event that contributes to a currently irreversible disease.