THUR 037 Identification of biofluid markers of TDP-43 pathology

IntroductionFrontotemporal dementia (FTD) is usually caused pathologically by either tau or TDP-43. Previous biofluid assays of TDP-43 have not so far proved to be sensitive or specific for identifying those cases with TDP-43 pathology.Material and methodsWe set out to investigate the novel TDP-43 Simoa assay (Quanterix) assay in both plasma and CSF in a cohort of patients recruited from the University College London FTD observational studies with known or likely TDP-43 pathology (17), non-TDP-43 pathology (13), and healthy controls (10).ResultsThe mean [standard deviation] plasma TDP-43 concentration was higher in those with likely TDP-43 pathology (155.1 [223.4] pg/ml) than those with non-TDP pathology (112.39 [252.9] pg/ml), and healthy controls (50.0 [23.1] pg/ml), but the differences between groups was non-significant, with substantial overlap in concentrations between all three groups. The mean CSF TDP-43 concentration was 2.9 [0.3] pg/ml in those with likely TDP-43 pathology, 2.8 [0.4] pg/ml in those with non-TDP pathology, and 3.1 [0.5] pg/ml in healthy controls. DiscussionThe assay tested in this study does not accurately distinguish between those with likely TDP-43 pathology and either disease controls or healthy individuals. There remains an urgent need to develop a better biofluid assay for pathological TDP-43.