Fig. 3

TDP-43 active immunization does not prevent weight loss, but the pTDP-43 antigen moderately lowers NfL. Body weight and NfL levels were analyzed in immunized control and rNLS8 mice. A Development of body weight in control and rNLS8 mice before and after transgene induction using doxycycline withdrawal. Mean values are plotted group-wise, n as indicated. The longitudinal effects of treatment (peptide immunization vs. no immunization), genotype (control vs. rNLS8), age as well as their interactions were analyzed using a three-way repeated measures ANOVA. On doxycycline chow, only age had a statistically significant effect on the body weight (p = 1.99*10^–102), but not the treatment (p = 0.74). After transgene induction, genotype (p = 0.018), age (p = 2.34*10^–26), and their interaction (p = 2.20*10^–26), but not treatment (p = 0.901), had a statistically significant effect on the body weight. B Comparison of the percentage body weight (BW) loss from transgene induction (25.5 weeks of age) to end-stage (28.5 weeks of age) against the TDP-PBS group using pairwise t-test with Benjamini–Hochberg correction revealed a statistically significant difference for both monogenic groups (ctrl PBS vs. TDP-PBS: p = 1.47*10^–11, ctrl VAX vs. TDP-PBS: p = 6.38*10^–10) only. Group means are indicated as black dots. C Neurofilament light chain (NfL) levels in the serum of end-stage mice were quantified using the Simoa® platform. Comparisons against TDP-PBS mice using pairwise Wilcoxon test with Benjamini–Hochberg correction revealed a statistically significant difference in NfL levels for ctrl PBS (p = 8.3*10^–7), ctrl VAX (p = 8.3*10^–7), and TDP15 immunized mice (p = 0.013). Mean values are indicated as black dots