Having detected pre-symptomatic skin TDP-43 pathology, ranging from 0.5–11 years before motor symptom onset, from all 7 individuals in our discovery cohort of peripheral tissue biopsies, we established an expanded biomarker validation cohort for skin to further investigate the prevalence and chronological range of TDP-43 pathology detectable in skin prior to motor symptom onset in people who went on the develop ALS. Here, TARDBP is linked to amyotrophic lateral sclerosis.