Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values &gt;0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.</p

The Effects of Surface Composition on 6-weeks of Plyometric Training

Background: Plyometric training programs may be performed on a hard surface or a soft surface to target specific training adaptations and enhance jump performance. However, it is unknown how surface compliance impacts jump performance. Objective: To compare changes in horizontal lower body power following a 6-week plyometric training program performed on a soft surface (n = 9) and a hard surface (n = 11). Methods: This was a quasi-experimental study. University students (N = 20; males = 11, females = 9; age: 20.4 ± 3.7 yr; body mass: 68.4 ± 12.5 kg; height 1.7 ± 0.1 m) with a history of being physically active volunteered to participate. Participants performed an initial pre-test standing long jump (SLJ), measured in centimeters (cm), then went through an accommodation period to be familiarized with training demands. A post-accommodation pre-test for SLJ was then completed. After the accommodation period, a 6-week plyometric training program was conducted. Following the completion of the training, a post-test was performed. The SLJ distance was analyzed with a 2 (surface) x 2 (time) repeated measures ANOVA. Results: There was no interaction for surface, but there was a main effect for time. Both training groups improved jump distance from pre- (soft surface = 191.6 ± 34.6 cm, hard surface = 216.1 ± 25.4 cm) to post-test (soft surface = 205.7 ± 38.8 cm, hard surface = 227.2 ± 23.4 cm). Conclusion: Practitioners designing plyometric training programs to increase lower body horizontal power may perform the training sessions on a soft surface or a hard surface and see similar improvements in horizontal jump performance