Figure 8: Pathological and behavioral consequences of chronic endothelial TDP-43 loss.

(A) Representative immunofluorescence images of fibrin deposition in mouse brain frontal cortex sections from 8–11-month-old mice (n=3 BrEC-KO and n=3 littermate controls) are shown. (C, E) Iba1 staining of microglia in the mouse brain cortex reveals consistent results across n=3 BrEC-KO and n=3 littermate controls mice (n=3), as well as n=3 Grn^R493X/+ and n=3 littermate controls mice (n=3) and (G, I) GFAP staining of astrocytes reveals a substantial increase in astrocyte numbers, resembling astrogliosis observed in FTD. (K, L) Behavioral Testing: Tube dominance test results for BrEC-KO mice and Grn^R493X/+ mice, showing a high “loss” percentage in both models. (B) Quantification of data, with each data point representing the fluorescence image intensity in one image. (D, F, H, J) Quantification of data with each data point representing the number of activated cells in an image. multiple images per mouse. Scale bars, 50 μm. Data are presented as means ± SEM. Statistical analysis was conducted using an unpaired Mann Whitney test, with significance levels indicated as follows: ****P<0.0001.