Figure 10.

TDP-43 stimulates tau phosphorylation and BACE1 expression. a, Knockdown of TDP-43 reduces phosphorylated GSK3β and prevents tau phosphorylation in cultured hippocampal neurons from tau TG mice (PS19). Hippocampal neurons in culture were treated with LV expressing TDP-43-shRNA or scramble control. The data are means ±SEM. *P<0.05, **P<0.01 compared with WT-LV-Scr; §§P<0.01 compared with Tau-TG-LV-Scr (ANOVA with Fisher's PLSD test post-hoc test, n=3). b, Silencing of GSK3β attenuates tau phosphorylation but does not affect TDP-43 expression in cultured hippocampal neurons from PS19 mice. Hippocampal neurons in culture were treated with LV expressing scramble control or GSK3β-shRNA. The data are means ±SEM. **P<0.01 compared with WT-LV-Scr; §§P<0.01 compared with Tau-TG-LV-Scr (ANOVA with Fisher's PLSD test post-hoc test, n=3). c, Immunoblot analysis of co-immunoprecipitation (co-IP) of BACE1 with TDP-43 in hippocampal tissues from WT mice (n=3 animals/group). d, Silencing of TDP-43 reduces expression of TDP-43 in hippocampal neurons cultured from 5xFAD mice. Hippocampal neurons in culture were treated with LV expressing TDP-43-shRNA or scramble control for three days. The data are means ±SEM. **P<0.01, ***P<0.001 compared with WT-LV-Scr; §§P<0.01 §§§P<0.001 compared with APP-TG-LV-Scr (ANOVA with Fisher's PLSD test post-hoc test, n=3).