Scoring of neuronal TMEM106B protein expression. (a) Scoring schema used to grade severity of disorganization of neuronal TMEM106B expression. Scores of 0 were assigned to sections in which almost all neurons displayed cytoplasmic TMEM106B expression with a vesicular pattern exhibiting a polarized quality. Nuclear boundaries were clear. Scores of 1 were assigned to sections in which a sizeable number of neurons displayed more diffuse TMEM106B staining dispersed more widely in the cytoplasm, but still delimited to the soma. Polarity was still usually maintained. Scores of 2 were assigned to sections in which most neurons recapitulated the characteristics of a score of 1. However, these sections also contained rare, non-degenerating neurons which displayed highly disorganized and diffuse TMEM106B staining throughout the cytoplasm with extension into processes. Scores of 3 were assigned to sections in which numerous neurons displayed highly disorganized and diffuse TMEM106B staining, with extension into processes. Scale bar represents 30 um. (b) Shown is the average scoring of the degree of diffuse neuronal TMEM106B expression by two independent, blinded scorers for N2077-stained human frontal cortical samples. Normal cases n = 7; Alzheimer’s disease n = 5; FTLD-tau n = 6, GRN (−) FTLD-TDP n = 5, GRN (+) FTLD-TDP n = 6. The colors in the dot plot correspond to the groups delineated in the bar graph. Weighted kappa = 0.44. GRN (+) FTLD-TDP cases demonstrated more disorganized patterns of TMEM106B expression (p = 0.005 for Mann–Whitney test).