Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20–85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Log_e NfL as a continuum, one standard deviation of Log_e NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60–2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.

神经丝轻链 （NfL） 是一种神经元特异性结构蛋白，在神经轴突损伤后释放到细胞外空间，包括体液。尽管有证据表明与神经系统疾病有关，但很少有研究在基于人群的研究中检查血清 NfL 与死亡率的相关性。利用了来自全国健康和营养调查的数据，包括 2,071 名非西班牙裔白人、非西班牙裔黑人和西班牙裔成年参与者以及其他种族群体（20-85 岁）的成年参与者，他们进行了血清 NfL 测量≤ 6 年，直到 2019 年。我们测试了血清 NfL 与总人群死亡率的相关性，并按性别分层，并增加了心脏代谢危险因素和营养生物标志物的潜在交互和中介作用。与总样本中低于中位 NfL 组相比，血清 NfL 水平升高 （高于中位组） 与死亡风险相关 （P = 0.010），在每个性别组内观察到趋势 （P < 0.10）。当将 Log_e NfL 作为一个连续体进行检查时，Log_e NfL 的一个标准差与死亡风险增加相关（HR = 1.88,95% CI 1.60-2.20，P < 0.001）在针对年龄、性别、种族和贫困收入比率调整的简化模型中; 这一发现仅随着生活方式和健康相关因素的调整而略有减弱。四向分解表明，除其他外，NfL 和 HbA1c 之间存在介导的相互作用，并且在预测全因死亡率方面与 25（OH）D3 存在纯粹不一致的中介作用，在针对所有其他协变量进行调整的模型中。 此外，尿白蛋白/肌酐比值与 NfL 在加法和乘法量表上的死亡风险方面协同作用。这些数据表明，在具有全国代表性的美国成年人样本中，血清 NfL 水平升高与全因死亡率相关。