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. 2021 Dec 27;145(10):3582–3593. doi: 10.1093/brain/awab478

Figure 4.

Figure 4

Tight junctions are impaired in ApoE4 mice along with MMP9 expression. (A and B) Electron microscopy analysis shows that APOE4 mice show an increased distance (as indicated by a small line) between membranes at tight junctions (white arrows) and that this is ameliorated in APOE4 astrocyte knockout mice both when compared at the mouse level F(3,11) = 5.926 P = 0.0117 and (C) the individual tight junction F(3,94) = 3.314 P = 0.0233. (D) However, we saw no different in the thickness of the endothelium. (E) Analysis of whole brain mRNA show that APOE4 animals have significantly higher expression of MMP9 compared with APOE3 animals but that knock of APOE4 from astrocytes reduces MMP9 expression to the level of APOE3 animals, APOE3 knockout has no effect F(3,32) = 8.153 P = 0.0004. (F) There is a correlation between APOE4 expression and MMP9 expression (P = 0.0021) but no correlation between these genes in APOE3 mice. (G) Analysis of protein whole brain by western blot shows that there is an increase in MMP9 protein in APOE4 animals compared with APOE3 animals and that astrocyte knock out reduces the MMP9 protein levels of APOE3 animals F(3,11) = 6.115 P = 0.0106. (H) There is a positive correlation at the protein level between APOE4 expression and MMP9 expression (P = 0.0018) and a negative correlation between these genes in APOE3 mice (P = 0.0418).