Amyloid beta peptides (Aβ) from Alzheimer's disease neuronal secretome induce endothelial activation in a human cerebral microvessel model.

Yu Jung Shin, Kira M Evitts, Solhee Jin, Caitlin Howard, Margaret Sharp-Milgrom, Tiara Schwarze-Taufiq, Chizuru Kinoshita, Jessica E Young, Ying Zheng

Neurobiology of disease 2023 Jun 01

filter terms:

In Alzheimer's disease (AD), secretion and deposition of amyloid beta peptides (Aβ) have been associated with blood-brain barrier dysfunction. However, the role of Aβ in endothelial cell (EC) dysfunction remains elusive. Here we investigated AD mediated EC activation by studying the effect of Aβ secreted from human induced pluripotent stem cell-derived cortical neurons (hiPSC-CN) harboring a familial AD mutation (Swe+/+) on human brain microvascular endothelial cells (HBMECs) in 2D and 3D perfusable microvessels. We demonstrated that increased Aβ levels in Swe+/+ conditioned media (CM) led to stress fiber formation and upregulation of genes associated with endothelial inflammation and immune-adhesion. Perfusion of Aβ-rich Swe+/+ CM induced acute formation of von Willebrand factor (VWF) fibers in the vessel lumen, which was attenuated by reducing Aβ levels in CM. Our findings suggest that Aβ peptides can trigger rapid inflammatory and thrombogenic responses within cerebral microvessels, which may exacerbate AD pathology. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Yu Jung Shin, Kira M Evitts, Solhee Jin, Caitlin Howard, Margaret Sharp-Milgrom, Tiara Schwarze-Taufiq, Chizuru Kinoshita, Jessica E Young, Ying Zheng. Amyloid beta peptides (Aβ) from Alzheimer's disease neuronal secretome induce endothelial activation in a human cerebral microvessel model. Neurobiology of disease. 2023 Jun 01;181:106125