Fig. 1

TDP-43 cytoplasmic mislocalization and deposition in the vulnerable ventral spinal cord of ALS cases. a Both pan and phosphorylated (p)TDP-43 antibodies identified diffuse cytoplasmic TDP-43 staining (arrows), as well as punctate (dotted arrowheads), globular (single downwards arrowheads) and fibrillar skein-like (double downwards arrowheads) TDP-43-immunopositive inclusions, in ventral spinal cord motor neurons of all ALS cases and a small proportion of controls. Pan TDP-43 immunostaining also revealed nuclear TDP-43 (open arrowheads) in ventral spinal cord motor neurons of ALS cases and controls. Case numbers (Additional file 1: Table S1) are listed in the top left corner of each panel. b, c The proportion of motor neurons possessing diffuse cytoplasmic TDP-43 or cytoplasmic TDP-43 inclusions (collectively termed TDP-43 pathology) was higher in ALS cases compared with controls (b; One-way ANOVA with Holm-Sidak’s multiple comparisons post-hoc tests; SOD1-fALS: p = 0.05; non-SOD1-fALS: p < 0.0001; sALS: p < 0.0001), whereas the proportion of motor neurons exhibiting nuclear TDP-43 immunostaining was significantly reduced in ALS cases compared with controls (c; One-way ANOVA with Holm-Sidak’s multiple comparisons post-hoc tests, p < 0.0001 for all comparisons). Data in b and c represent mean ± SEM. *p < 0.05, ****p < 0.0001. d Phosphorylated (p)TDP-43 pathology is absent within control, SOD1-fALS and sALS spinal cord motor neurons exhibiting non-pathological nuclear TDP-43 (open arrowheads) and granular SOD1 immunostaining (closed arrowheads). Scale bars in a and d represent 25 µm. Antibody details are listed in Additional file 1: Table S3. No immunostaining was observed in spinal cord tissue sections processed as above in the absence of primary antibodies (Additional file 1: Figure S1)