Figure 2.

Anti-TDP-43 C-t antibodies detect more neuropathology than N-t antibodies in dentate gyrus and frontal cortex of FTLD-U subtypes. A-F: Adjacent sections of hippocampal tissue from FTLD-U cases show robust labeling of neuronal cytoplasmic inclusions (arrowheads) in the dentate gyrus (DG) using both pan TDP-43 antibody (A and D) and C-t TDP-43 pAb (B and E), in contrast to marginal staining with N-t TDP-43 pAb (C and F). D–F: High-power views of the fields depicted in A–C. Note clearing of nuclear TDP-43 (arrows) in inclusion-bearing neurons compared with that of nonaffected neurons (*). G–O: Adjacent sections of frontal cortex (FC) in FTLD-U cases show the characteristic features of type I pathology (G–I), with long and tortuous dystrophic neurites with relatively few neuronal cytoplasmic inclusions and no neuronal intranuclear inclusions. Type II cases (J–L) present numerous cytoplasmic inclusions and infrequent neuritic profiles. Type III cases (M–O) have numerous neuronal cytoplasmic inclusions and dystrophic neurites and occasional intranuclear inclusions in lamina II. Note the similar immunoreactivity pattern of characteristic TDP-43 pathology, ie, cytoplasmic inclusions (arrowheads) and dystrophic neurites, for pan TDP-43 pAb (G, J, and M) and C-t TDP-43 pAb (H, K, and N). Use of N-t TDP-43 pAb (I, L, and O) revealed remarkably reduced staining for both types of pathology (arrows) but robust nuclear staining of normal cells. Insets in J–O show a high-power detail of representative staining. Scale bars: 25 μm (A–C and G–O); 7 μm (D–F and insets in J–O).