Fig. 7
RBM45 subcellular distribution and inclusion pathology in FTLD-TDP, ALS, and AD. Immunohistochemistry for RBM45, SAFB, and TDP-43 was performed in hippocampal dentate gyrus from non-neurologic disease control, FTLD-TDP, ALS, and AD subjects. a Control subjects showed strong immunoreactivity for SAFB, TDP-43, and RBM45, with RBM45 immunoreactivity concentrated in the perinucleolar region (arrowheads) and SAFB and TDP-43 diffusely localized throughout the nucleus. b RBM45 immunoreactivity was predominantly in nuclear inclusions in FTLD dentate gryus cells, with attendant loss of cytoplasmic and perinucleolar immunoreactivity. Nuclear RBM45 inclusions lack SAFB and TDP-43. Dentate gyrus cells containing RBM45 nuclear inclusions also exhibit reduced SAFB immunoreactivity. Several TDP-43 and RBM45-positive cytoplasmic inclusions were found in FTLD subjects (arrow). c As in (b), but for ALS subjects. Nuclear RBM45 inclusions lack SAFB or TDP-43, and cytoplasmic inclusions contain RBM45 and TDP-43 (arrow). d As in (b), but for AD subjects. Nuclear RBM45 inclusions lack SAFB and TDP-43, and cytoplasmic inclusions contain RBM45 and TDP-43 (arrow). e Boxplot showing the number of RBM45 nuclear inclusions by group (# = p < 0.01, * = p < 1 × 10− 6). f Stacked bar plot showing the number of RBM45 nuclear inclusions per cell by subject group. Most dentate gyrus cells from control subjects have no inclusions, while FTLD-TDP, ALS, and AD subjects have significantly more granules per cell across the range of observed values. g The relationship between RBM45 nuclear inclusions and SAFB immunoreactivity is shown, along with the regression line. Regardless of disease state, with increasing numbers of RBM45 nuclear inclusions, SAFB immunoreactivity decreases, particularly at ≥3 granules per cell. The relationship between these two variables is statistically significant (p < 1 × 10− 16). In the scatterplot shown, jitter is added to the points to more clearly visualize the data, but the separation between inclusion integer numbers is still seen. The inset image shows an example of adjacent cells in an FTLD-TDP subject where one cell with no RBM45 granules has strong SAFB nuclear immunoreactivity, while the neighboring cell has several nuclear RBM45 inclusions and low SAFB nuclear immunoreactivity. In (a-d), the scale bar = 20 μm, while in the inset in (g) the scale bar = 5. For all panels, FTLD = FTLD-TDP