Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Department of Neurology, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Ann Clin Transl Neurol. 2024 May;11(5):1347-1358. doi: 10.1002/acn3.52054. Epub 2024 Apr 8.
To model interdependencies of serum neurofilament light chain (sNfL), a clinically useful biomarker of axonal injury in neurological diseases, with demographic, anthropometric, physiological, and disease biomarkers in the United States population.
sNfL and 80 biomarkers were obtained from the National Health and Nutrition Examination Survey (n = 2071, age: 20-75 years). Body habitus and composition, electrolytes, blood cell, metabolic, liver, and kidney function biomarkers, and common diseases were assessed with weighted regression adjusted for age, sex, and race/ethnicity. Salient biomarkers were modeled with ensemble learning; a Bayesian network structure was obtained for interdependencies.
Age was strongly associated with sNfL. sNfL levels were 13% higher in men versus women. Mexican Americans had 18.5% lower sNfL versus Non-Hispanic Whites. sNfL was similar in pregnant versus nonpregnant women. Lymphocyte, and neutrophil numbers, and phosphorus, and chloride levels were associated with sNfL. Multiple liver function (e.g., albumin and gamma-glutamyltransferase), renal function (e.g., creatinine and urea), and carbohydrate/lipid metabolism markers (e.g., glucose and triglycerides) were associated with sNfL. A 50% greater creatinine was associated with 26.8% greater sNfL. Diabetes, kidney disease, congestive heart failure, and stroke were associated with sNfL. The ensemble learning algorithm predicted high sNfL outliers with 5.06%-9.16% test error. Bayesian network modeling indicated sNfL had neighbor dependencies with age, creatinine, albumin, and chloride.
sNfL is associated with age, kidney and liver function, diabetes, blood cell subsets, and electrolytes. sNfL may be a useful biomarker for biological age of the whole body and major organ systems including the brain.
建立美国人群中血清神经丝轻链（sNfL）与人口统计学、人体测量学、生理学和疾病生物标志物之间的相互依赖关系模型，sNfL 是神经疾病中轴突损伤的一种有临床应用价值的生物标志物。
从国家健康和营养调查（n=2071，年龄 20-75 岁）中获取 sNfL 和 80 种生物标志物。使用加权回归方法评估体重指数和成分、电解质、血细胞、代谢、肝和肾功能生物标志物以及常见疾病，调整了年龄、性别和种族/民族因素。使用集成学习对显著生物标志物进行建模；获得了相互依赖关系的贝叶斯网络结构。
年龄与 sNfL 密切相关。男性的 sNfL 水平比女性高 13%。与非西班牙裔白人相比，墨西哥裔美国人的 sNfL 低 18.5%。怀孕与未怀孕女性的 sNfL 相似。淋巴细胞和中性粒细胞数量以及磷和氯水平与 sNfL 相关。多种肝功能（如白蛋白和γ-谷氨酰转移酶）、肾功能（如肌酐和尿素）和碳水化合物/脂质代谢标志物（如葡萄糖和甘油三酯）与 sNfL 相关。肌酐增加 50%，sNfL 增加 26.8%。糖尿病、肾病、充血性心力衰竭和中风与 sNfL 相关。集成学习算法预测 sNfL 高值异常值的测试误差为 5.06%-9.16%。贝叶斯网络模型表明，sNfL 与年龄、肌酐、白蛋白和氯有邻居依赖关系。
sNfL 与年龄、肾功能和肝功能、糖尿病、血细胞亚群和电解质有关。sNfL 可能是全身和包括大脑在内的主要器官系统生物年龄的有用生物标志物。
