Fig. 2
From: TDP-43 pathology is associated with increased tau burdens and seeding
The presence of LATE-NC associates with exacerbated tau seeding in vitro. A tau (P301S) biosensor cell line was transfected with sarkosyl-insoluble homogenates of entorhinal and frontal cortex from 5 controls, 8 AD(LATE-NC-), 11 AD(LATE-NC+) and 5 FTLD-TDP cases. After 48 h, the number of spots/cell (p-tau signal) were automatedly quantified (a). At a dilution of 1:20, cells treated with entorhinal cortex extracts from AD(LATE-NC+) cases showed increased p-tau seeding compared to FTLD-TDP and control-treated extracts (b). Similarly, cells transfected with frontal cortex homogenates from AD(LATE-NC+) cases display increased seeding compared to controls, AD(LATE-NC-) and FTLD-TDP treated cells (c). One-way ANOVA with Tuckey’s correction was used. Overview of each experimental condition is displayed in (d), scale bars = 50µm. Immunoprecipitation of pTDP-43 (S409/S410) from sarkosyl-insoluble homogenates shows a significant decrease of TDP-43 (350-414aa., ThermoFisher Scientific) and p-tau396/404 in the non-bound fractions (e). When cells are treated with pTDP-43-depleted fractions from 4 controls, 2 AD(LATE-NC-) and 7 AD(LATE-NC+), p-tau seeding was significantly reduced in the AD(LATE-NC+) group, compared to cells treated with the corresponding non-depleted homogenate (f), Wilcoxon matched-pairs signed ranked test