Abeta peptides disrupt the barrier integrity and glucose metabolism of human induced pluripotent stem cell-derived brain microvascular endothelial cells

Amyloid β (Aβ) peptides are key components of Alzheimer's disease and cerebral amyloid angiopathy and have been associated with detrimental effects at the blood-brain barrier (BBB) in vivo. Yet, the cellular and molecular mechanisms by which such peptides exert their effect on the brain vasculature remain unclear. This study aimed to assess the cellular response of induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) to Aβ peptides. Changes in the barrier function, efflux transporters activity, glucose uptake, and metabolism were assessed in such model. Although iPSC-derived BMECs sustained prolonged exposure (<72 h) to a high level of Aβ peptides including Aβ42, such cells also suffered from a loss of barrier integrity, coupled with reduced glucose uptake and impaired bioenergetic activity. Taken together, this study shows the ability of iPSC-derived BMECs to reproduce features observed in other models and suggests that Aβ peptides may compromise the BBB via different targets.