VEGF receptor-1 modulates amyloid β 1-42 oligomer-induced senescence in brain endothelial cells

Aggregated amyloid β (Aβ) peptides in the Alzheimer’s disease (AD) brain are hypothesized to trigger several downstream pathologies, including cerebrovascular dysfunction. Previous studies have shown that Aβ peptides can have antiangiogenic properties, which may contribute to vascular dysfunction in the early stages of the disease process. We have generated data showing that brain endothelial cells (ECs) exposed to toxic Aβ1-42 oligomers can readily enter a senescence phenotype. To determine the effect of Aβ oligomers on brain ECs, we treated early passaged human brain microvascular ECs and HUVECs with high MW Aβ1-42 oligomers (5 µM, for 72 h). For controls, we used no peptide treatment, 5 µM Aβ1-42 monomers, and 5 µM Aβ1-42 fibrils, respectively. Brain ECs treated with Aβ1-42 oligomers showed increased senescence-associated β-galactosidase staining and increased senescence-associated p21/p53 expression. Treatment with either Aβ1-42 monomer or Aβ1-42 fibrils did not induce senescence in this assay. We the...