Fig. 5

(A) Quantification of Tau Puncta (TP) in Tau-GBA1^WT(XX) and Tau-GBA1^{L444P/L444P(I)}α fibroblasts at basal conditions (mean ± sem normalized on Tau-GBA^WT(XX), n = 55–60). Mann-Whitney test, *** p 0.0004. (B) Quantification of Tau puncta in Tau-GBA1^{L444P/L444P(I)}α fibroblasts treated overnight in the absence (ctrl) or presence (seeds) of Alzheimer’s brain-derived Tau seeds (mean ± sem normalized on ctrl, n = 45). Mann-Whitney test, **** p 4 × 10^− 11. A representative image of ctrl or Tau seeds conditions are shown (Tau in magenta, nuclei stained with DAPI in blue). (C) GCase activity in Tau-GBA1^{L444P/L444P(I)}α fibroblasts treated overnight in the absence or presence of Tau seeds (mean ± sem normalized on ctrl, n = 3). Mann-Whitney test, not significant. (D) as in B. for Tau-GBA1^WT(XX) fibroblasts (n = 45). Mann-Whitney test, **** p 0.00001. (E) as in C. for Tau-GBA1^WT(XX) fibroblasts (n = 6–9). Mann-Whitney test, not significant. (F) Dose-dependent reduction of Tau Puncta in Tau- GBA1^{L444P/L444P(I)}α fibroblasts or (G) in GBA1^WT(XX) fibroblasts treated for 4 days with the indicated amount of GT-02216 (mean ± sem normalized on vehicle, no seed ctrl, n = 15–45). 2way ANOVA (p < .0001 for GT-02216 concentration and seeds) and Šídák’s multiple tests against vehicle, **** p < .0001.