HBEC Tau-V5 - Composite copy.tiff

Brain vascular endothelial cell senescence in Alzheimer's disease

Figure 4 Hussong et al tau in EC.jpg
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Soluble tau aggregates induce senescence/SASP in primary human brain microvascular endothelial cells. (A-C) Soluble tau aggregates trigger increases in cell and nuclear size in primary human brain microvascular endothelial cells (HBEC). A, Representative images of HBEC treated with recombinant human cytokeratin-8 (KRT8), monomeric tau protein (M. Tau), soluble tau aggregates (O.Tau), or vehicle. B, Quantitative analyses of cell size (H=9.264, P=0.026, *) and C, nuclear area (H=7.989, P=0.046, *) of HBEC represented in A (n=4-8). (D-F) Soluble tau aggregates trigger cell cycle arrest in HBEC. D, Quantitative real-time PCR (qRT-PCR) measurements of mRNA abundance for cyclin dependent kinase inhibitor 2A (Cdkn2a (F(3,22)=5.264, P=0.007, **); E, Cyclin dependent kinase inhibitor 1A (Cdkn1a, F(3,23)=7.545, P=0.0011, **), and F, Tumor protein 53 (Tp53, (F(3,23)=3.050, P<0.05, *). (G-K)Soluble tau aggregates promote expression of the senescence-associated secretory phenotype in HBEC. G,interleukin 6 (IL-6, F(3,22)=147.7, P<0.0001, ****); H, interleukin 1β (IL-1β, H=16.49, P=0.0009, ***); I, tumor necrosis factor (TNF, F(3,21)=14.85, P<0.0001, ****); J, monocyte chemoattractant protein-1(MCP-1, F(3,22)=12.44, P<0.0001, ****), and K, plasminogen-activator inhibitor-1 (PAI-1, F(3,22)=4.173, P=0.018, *), ANOVA or Kruskall-Wallis analysis, n=3-16. Data are representative images and means ± SEM.