Extended Data Fig. 1: TDP-43 peripheral pathology in SOD1 patients and SOD1 mouse models.

a) Immunofluorescent staining for pTDP-43 in intramuscular nerves within muscle biopsies of non-ALS (spinal stenosis), SOD1 (c.26 T > A), and sALS patients. Blue indicates NFH, Gray indicates pTDP-43 and colocalized pTDP-43 within NFH positive nerves (in the respective panel). Scale bar: 5 µm. b) Representative immunofluorescent images of TDP-43 in sciatic nerve longitudinal sections of SOD1^G93A mice and their littermates (LM). Gray indicates TDP-43 and NFH-masked TDP-43 (in the respective panel), blue indicates NFH. Scale bar: 10 µm. c) Representative images of TDP-43 immunolabeling in sciatic nerve cross sections of p290 SOD1^G37R mice and their littermates. Gray indicates TDP-43 and NFH-masked TDP-43 (in the respective panel), blue indicates NFH, yellow indicates S100β. Scale bar: 10 µm. d) Quantitative analysis of TDP-43 intensity within S100β region in sciatic nerve sections of p290 SOD1^G37R mice and their littermates. Data is shown as the mean TDP-43 intensity in S100β mask ± SD. n = 26; 29 images from 3 mice in each condition. Two-tailed unpaired student’s t-test. ****p = 2.11×10⁻⁶. e) Representative images of pTDP-43 immunolabeling in sciatic nerve cross sections of p290 SOD1^G37R mice and their littermates. Gray indicates pTDP-43 and NFH-masked pTDP-43 (in the respective panel), blue indicates NFH, yellow indicates S100β. Scale bar: 10 µm. f) Quantitative analysis of pTDP-43 intensity within S100β region in sciatic nerve sections of p290 SOD1^G37R mice and their littermates. Data is shown as the mean pTDP-43 intensity in S100β mask ± SD. n = 27; 29 images from 3 mice in each condition. Two-tailed unpaired student’s t-test. **p = 0.0018. For a, immunofluorescent labeling for pTDP-43 in SOD1 patient repeated once for 1 patient. Labeling on non-ALS and ALS patients was repeated for 6 patients and 6 healthy controls. For b, representative images of experiment repeated in 3 mice per genotype.