Fig. 6

Differential vulnerability of glial cells in the ALS primary motor cortex. Olig2+ OPC (a) and mature TPPP/p25+ oligodendrocytes (b) were present in all layers of the primary motor cortex. Red arrow in (a) indicates satellite oligodendrocyte surrounding the apical dendrite of a Betz cell (green asterisks). There was no difference in the numbers of mature or immature oligodendrocytes between ALS and control cases (e, f). pTDP-43 inclusions are present in oligodendrocytes (c, red arrows indicated by characteristic ‘comma’ shaped inclusions) and neurons (d, red arrows indicate neuronal pTDP). Both the mean numbers of oligodendroglial inclusions and the relative predominance of pTDP-43 oligodendroglial pathology was higher in C9-ALS, but was not statistically higher than in sporadic disease (g, h). This relative distribution was confirmed qualitatively using double staining for pTDP-NeuN (i, j) and pTDP-Olig2 (k-l, green arrow indicates Olig2-negative neuronal inclusion). Multiplexed immunofluorescence reveals that Iba1+ microglia (m-p, green arrow in m indicates Iba1+ microglia extending processes to surround large layer V neuron containing pTDP-43 aggregates) occasionally contain pTDP-43, but we could find no clear evidence of this in GFAP+ astrocytes (q-u), even in cases with severe pTDP-43 pathology overall. Bars on graphs (e-h) represent means and SD. Scale bars (μm): c, i = 25, j = 20; k, l, m = 10; all others = 50