Physical Activity is Related to Lower Levels of Neurofilament Light and Plasma Tau Protein: A 22-Year Follow-Up Study From Adolescence to Adulthood

Purpose: To investigate the association between physical activity (PA) and neurodegeneration biomarkers from adolescence to adulthood by examining tau protein and neurofilament light chain (NfL) levels in blood samples. Methods: The study analyzed data from adolescents aged 12–19 years who participated in Waves I (1994–1996) and V (2016–2018) of the Add Health study over a span of 22 years. It assessed PA through self-reported questionnaires. Neurodegeneration measures at Wave V used venous blood collected via phlebotomy. Samples were analyzed using single-molecule array (Simoa) technology on a Quanterix HD-1 analyzer, using digital enzyme-linked immunosorbent assay to quantify NfL and tau proteins from serum and plasma samples. Results: In the present study, 3,182 individuals participated, with females comprising 61% of the sample. Participants adhering to the PA guidelines in both waves reported lower levels of NfL (−0.583 pg/mL, 95% bias-corrected and accelerated (BCa) confidence interval (CI): −1.235 to −0.068) and tau protein levels (−0.244 pg/mL, 95% BCa CI: −0.405 to −0.078). Adjusted analyses confirmed significant lower levels of tau protein (−0.210 pg/mL, 95% BCa CI: −0.350 to −0.072) for Wave I adherents and even lower levels in NfL (−0.421 pg/mL, 95% BCa CI: −0.929 to −0.007) and tau protein levels (−0.229 pg/mL, 95% BCa CI: −0.412 to −0.053) for active participants in both waves. Discussion: Our findings suggest that consistent engagement in PA may reduce certain neurodegenerative biomarkers, potentially influencing neurological health outcomes.