Proteomics analysis of TDP-43 aggregates derived from HEK293A

97% of sporadic ALS patients exhibit pathology and aggregation of a global RNA regulator protein, transactive response DNA binding protein of 43 kDa (TDP-43). The goal of this study was to optimize and characterize a novel immuno-purification platform for ALS-associated TDP-43 aggregates using a scalable HEK293A culture model. Proteomics analysis was used to profile disease-associated post-translational modifications and TDP-43 co-aggregating proteins. Our findings support use of this protocol to generate pathologically relevant TDP-43 aggregates suitable for mechanistic studies in biochemical and cell-based assays.