Elevated Serum Neurofilament Light Chain Levels Are Associated With All-Cause Mortality: Evidence From National Health and Nutrition Examination Survey

Abstract Background Several studies have reported the association between blood neurofilament light chain (NfL) levels and all-cause mortality. However, the generalizability of these findings in general adults remains unclear. The study aimed to examine the association between serum NfL and all-cause mortality in a nationally representative population. Methods Longitudinal data were obtained from 2 071 participants aged 20–75 years in the National Health and Nutrition Examination Survey 2013–14 cycle. Serum NfL levels were measured by using a novel, high-throughput acridinium-ester immunoassay. Kaplan–Meier curves, multivariate Cox regression analysis, and restricted cubic spline regression were employed to investigate the association between serum NfL and all-cause mortality. Results Over a median follow-up of 73 (interquartile range = 12) months, 85 (3.50%) participants died. After adjustment for sociodemographic characteristics, lifestyle variables, comorbidity, body mass index, and estimated glomerular filtration rate, elevated serum NfL levels were still significantly associated with a higher risk of all-cause mortality (hazard ratio = 2.45, 95% confidence interval = 1.89–3.18 for per lnNfL increase) in a linear manner. Conclusions Our findings suggest that circulating levels of NfL may serve as a biomarker of mortality risk in a nationally representative population.