Fig. 4

Nucleolar volume is increased in RNA foci-bearing neurons in C9FTLD patient brain. a Representative images of frontal cortex from a heterozygous C9FTLD case immunostained for the nucleolar protein nucleophosmin (NPM, green), with RNA fluorescent in situ hybridisation for sense RNA foci (red) and DAPI nuclear stain (blue); typical RNA foci-bearing (Foci+) and non foci-bearing (Foci-) neurons are highlighted with dotted boxes. Scale bar represents 2 μm. b, c Quantification of neuronal nucleolar volume determined by nucleophosmin immunoreactivity. Frequency distribution of pooled C9FTLD (heterozygous cases) nucleolar volumes show a slight shift to increased volumes in neurons bearing RNA foci compared with neurons without foci (b). Median nucleolar volume in C9FTLD cases was significantly larger in neurons with RNA foci compared with neurons without foci inclusions (c). Each dot represents an individual heterozygous C9FTLD case, grey lines link medians from the same cases in neurons with or without RNA foci, and the average and SEM are shown as long and short horizontal bars, respectively. Significance was determined by paired regression analysis: *p < 0.05