Fig. 3

Patient-derived iMGs carrying GRN variants display abnormal TDP-43 aggregation. A Fluorescence images of IBA1 (purple, microglia), TDP-43 (red), pTDP-43 (Ser409/410, green) in FTD–GRN iMGs vs. controls; DAPI for nuclei. Scale bar, 10 µm. B Cytoplasmic TDP-43 in IBA1⁺ iMGs quantified, 50 + cells/subject, three experiments. Mean ± SEM; ****p < 0.0001 (one-way ANOVA, Tukey’s test). C Images of IBA1 (purple), TDP-43 (red), ubiquitin (green) in FTD–GRN iMGs. DAPI-stained nuclei. Scale, 10 µm. D Western blot for total/phosphorylated TDP-43 in FTD–GRN vs. control iMGs; GAPDH for soluble fraction. E Complement C1q concentration in CM by ELISA (n = 3); *p < 0.05, **p < 0.01 (one-way ANOVA with post hoc Tukey’s test). F TDP-43 and ubiquitin in BV2 cells post-siRNA GRN knockdown, with/without 1 μg/ml C1q for 24 h. DAPI nuclei. Scale, 10 µm. G. Quantification of cytoplasmic TDP-43 granules in condition (F), 50+ cells/condition, 3 experiments. Mean ± SEM; ****p < 0.0001