Fig. 1

Insoluble CHCHD10 aggregates accumulate and colocalize with phospho-TDP-43 inclusions in FTLD-TDP and AD patients’ brains. a–c Representative images of postmortem frontal cortex brain sections from healthy controls, FTLD-TDP, and AD cases immunostained for pS409/410-TDP-43 (green), CHCHD10 (red), and DAPI (blue). White boxes magnified in bottom panels. Colocalization of CHCHD10 with phospho-TDP-43 (yellow arrows), no colocalization (white arrows), and CHCHD10 aggregates larger than phospho-TDP-43 (red arrow). d, e Quantification of the pS409/410-TDP-43 (green) colocalization with CHCHD10 (red) (d), and CHCHD10 (red) colocalization with pS409/410-TDP-43 (green) (e) using Mander’s overlap coefficient (MOC, ImageJ) from FTLD-TDP and AD frontal cortex (t-test, **p < 0.01, n = 22 images from 4 FTLD-TDP cases, n = 19 from 3 AD cases). f Representative blots of TDP-43, CHCHD10, and actin from RIPA-insoluble frontal cortex brain extracts. g, h Quantification of RIPA-insoluble TDP-43 (l) and insoluble CHCHD10 (m) from human FTLD-TDP and nondemented control frontal cortex (t-test, ##P < 0.0001, n = 10 FTLD-TDP, n = 11 control). i Positive correlation between insoluble TDP-43 and insoluble CHCHD10 from FTLD-TDP and control frontal cortex (Linear regression, F = (1, 19) = 13.23, R² = 0.4104, P = 0.0018; Pearson’s r = 0.6407, n = 21). Blue line represents the slope and dashed lines the 95% confidence interval