Albeit we did not discriminate directly between exogenous and endogenous TDP-43 in recipient cerebral organoids, our results showing the reduction of nuclear TDP-43 and the time-dependent increase of pTDP-43 aggregates in the cerebral organoids administrated with ALS patient-derived protein extracts suggest that exogenous pathogenic TDP-43 acts as seeds and propagates cell-to-cell to form de novo TDP-43 pathology by altering normal endogenous TDP-43 to pathological conformations. Here, TARDBP is linked to amyotrophic lateral sclerosis.