High molecular weight TDP-43 band on SDD-AGE gels found in FTLD-TDP but not control brain homogenates.

<p>(A) Immunoblot of brain homogenates separated on an analytic SDD-AGE gel and probed with polyclonal anti-TDP-43 serum. Twenty-five µL of a 10% brain homogenate from the frontal or anterior temporal cortex was loaded in each lane. A slow-migrating band (upper bracket) is present only in the FTLD-TDP cases. Arrowheads indicate the position of molecular weight markers. The arrowhead labeled “titan” marks the position of the ∼ 3000-kDa titan band on a Coomassie-stained gel of chicken muscle extract on an SDD-AGE gel run under identical conditions. (B) Ratio of upper to lower band greater in FTLD than in controls. The quantities of TDP-43 in the range of the upper bracket and the lower bracket (Fig. 1A) were determined as described in the Methods, and then the ratio of the upper to the lower band calculated. This ratio is greater in every FTLD case than in any control and the difference between the two groups is significant (P = 0.013, one-way t-test). The plots depict the range (thin horizontal bars), median (white line) and 25–75 percentile range (box) of values. (C) TDP-43 in upper band correlates with FTLD diagnosis, not with total quantity of TDP in sample. Quantity of TDP-43 in the lower band plotted against that in the upper band. Filled circles are FTLD cases, open circles are control cases. While there appears to be a correlation of TDP-43 quantity in the upper region with that in the lower for FTLD cases, no such correlation exists for controls. Quantities in the lower region for FTLD cases and controls largely overlap.