Endurance Exercise Attenuates Plasma Level of Neurofilament Light Chain and Prevents Body Weight Loss in a Rat Model of Tauopathy.

Although its effectiveness and underlying mechanisms are not fully understood, regular physical exercise (PE) is a potential low-cost strategy to prevent or delay neurodegeneration. Plasma neurofilament light chain (NfL), an established biomarker of axonal damage, helps monitor the progression of neurodegenerative disease. Here, we tested whether moderate-intensity endurance exercise modulates body weight trajectories in a rat model of tauopathy expressing human truncated tau protein (WKY72) and how it is associated with plasma NfL. Three months old Wistar Kyoto (WKY) and tauopathic WKY72 rats underwent 10 weeks long treadmill training regimen (30 min/day, 5 days/week). NfL was quantified in plasma of experimental animals collected before the experiment, then after 4 and 8 weeks long training. Sedentary controls were tested in parallel. Body weights were recorded at the same intervals and additionally two weeks later. We found that sedentary WKY72 rats displayed a significant 8.9-fold increase in NfL, while trained WKY72 animals showed only a 3.8-fold increase (both p < 0.0001). In WKY rats, exercise paradoxically led to a modest yet significant increase in NfL (2.9-fold, p < 0.001). Moreover, PE prevented the late-stage weight loss observed in sedentary tauopathic rats. In conclusion, moderate-intensity endurance exercise attenuates plasma level of NfL in tauopathic rats, indicating the potential of exercise as a disease-modifying intervention. Our findings establish a framework for further mechanistic exploration of links between PE and neuroprotective processes. Key words Physical activity " Weight loss " Tauopathy " Neurofilament light chain.