Stress granules and ALS spinal cord inclusions form distinct cytoplasmic structures.
A, IHC was performed on lumbar spinal cord sections from sporadic ALS cases harboring TDP-43 pathology. B–E, TDP-43 inclusions were labeled with phosphorylated (P409/410) TDP-43 antibodies (red), and stress granules were marked by FMRP (B), P-FMRP (C), TIA-1 (D), or TIAR (E), antibodies (green). All ALS cases displayed spinal cord pathology, as assessed by phosphorylated 409/410 immunoreactivity. There was minimal co-localization of SG markers with either skein-like, round, or filamentous TDP-43 aggregates (see merged panels). The specificity of all SG antibodies was validated by SG immunoreactivity in arsenite-treated cells. Secondary evaluation of antibody specificity was tested by positive immunoreactivity in cells overexpressing FMRP, TIA-1, and/or TIAR. Scale bar, 200 μm. White arrows highlight neurons that are magnified in insets, and magenta arrowheads highlight TDP-43 inclusions.