TDP-43 levels are higher in platelets from patients with sporadic amyotrophic lateral sclerosis than in healthy controls

TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of ubiquitinated inclusions in motor neurons of sporadic amyotrophic lateral sclerosis (ALS). TDP-43 is ubiquitously expressed and the majority of TDP-43 is normally localized to the nucleus. In motor neurons of patients with ALS, TDP-43 is not localized in the nucleus, relocates to the cytoplasm, and accumulates as cytoplasmic inclusions. Based on recent reports that TDP-43 is increased in the cytoplasmic fraction of peripheral blood mononuclear cells in sporadic ALS, and several studies on platelet dysfunction in ALS patients, we investigated the TDP-43 levels in platelets from patients with sporadic ALS. We measured TDP-43 levels with a sandwich enzyme-linked immunosorbent assay in platelets separated from whole blood, and compared the TDP-43 level in platelets from sporadic ALS (n = 19) patients with platelets from non-ALS controls (n = 21). The TDP-43 concentration in platelets was significantly higher in patients with ALS compared to age-matched controls. According to sub-analysis, the TDP-43 concentration in platelets tended to increase in ALS patients with longer disease duration, as well as with lower score on the ALS Functional Rating Scale Revised (ALSFRS-R), though the differences were not statistically significant. These results suggest that ALS also affects platelets in addition to motor neurons.