Amyloid β aggregation induces human brain microvascular endothelial cell death with abnormal actin organization

Cerebral amyloid angiopathy (CAA) is a disease in which amyloid beta (A beta) is deposited on the walls of blood vessels in the brain, making those walls brittle and causing cerebral hemorrhage. However, the mechanism underlying its onset is not well understood. The aggregation and accumulation of A beta cause the occlusion and fragility of blood vessels due to endothelial cell damage, breakdown of the blood-brain barrier, and replacement with elements constituting the blood vessel wall. In this study, we observed the effect of A beta on human primary brain microvascular endothelial cells (hBMECs) in real-time using quantum dot nanoprobes to elucidate the mechanism of vascular weakening by A. It was observed that A beta began to aggregate around hBMECs after the start of incubation and that the cells were covered with aggregates.A beta aggregates firmly anchored the cells on the plate surface, and eventually suppressed cell motility and caused cell death. Furthermore, A beta aggregation induced the organization of abnormal actin, resulting in a significant increase in intracellular actin dots over 10 mu m(2). These results suggest that the mechanism by which A beta forms a fragile vessel wall is as follows: A beta aggregation around vascular endothelial cells anchors them to the substrate, induces abnormal actin organization, and leads to cell death.