神经丝轻链蛋白在阿尔茨海默病早期诊断中的作用研究

Role of neurofilament light chain protein in the early diagnosis of Alzheimer's disease

摘要:

目的： 探讨血清神经丝轻链蛋白（neurofilament light chain protein，NFL）是否可以作为预测阿尔茨海默病（Alzheimer's disease，AD）早期的外周血生物标志物。 方法： 纳入新疆医科大学附属中医医院阿尔茨海默病临床数据库的AD患者50例，遗忘型轻度认知功能障碍（amnestic mild cognitive impairment，aMCI）患者50例，以及选择同一时间段内按年龄、文化程度相匹配的健康对照者（cognitively normal，CN）50例，受试者均采集血清，采用酶联免疫吸附试验（enzyme linked immunosorbent assay，ELISA）检测血清NFL水平。 结果： ①AD、aMCI与CN患者的年龄、教育年限、体质指数（body mass index，BMI）比较均无统计学差异（P>0.05），资料具有可比性。②AD患者简易精神状态检查量表（mini-mental state examination，MMSE）、蒙特利尔认知评估量表（Montreal cognitive assessment，MoCA）评分显著低于aMCI组和CN组[AD组（17.48±7.50），aMCI组（25.56±1.63），CN组（28.60±1.09）；F=81.830，P=0.000]，MoCA评分差异最明显[AD组（12.04±6.31），aMCI组（19.92±3.17），CN组（27.62±1.16）；F=177.187，P=0.000]。③血清NFL水平[AD组（4.486±2.463）ng/mL，aMCI组（5.101±2.172）ng/mL，CN组（2.885±1.469）ng/mL，F=15.167，P=0.000]，AD组和aMCI组NFL水平显著高于CN组，其中aMCI组最高，3组间比较具有统计学差异；应用Spearman相关性分析发现3组间年龄、MMSE评分、MoCA评分、日常生活能力量表评分（activity of dai1y living scale，ADL）、临床痴呆评定量表（clinical dementia rating，CDR）评分与NFL水平没有相关性（P>0.05）。 结论： 轻度认知功能障碍患者血清NFL水平最高，提示血清NFL也许是预测阿尔茨海默病早期的外周血生物标志物。

Abstract:

Objective: To explore whether serum neurofilament light chain protein (NFL) can be used as a peripheral blood biomarker to predict the early stage of Alzheimer's disease (AD). Methods: The study included 50 AD patients (AD group) from the Alzheimer's disease clinical database of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, 50 patients with amnestic mild cognitive impairment (aMCI group) and the same time period 50 cognitively normal controls (CN group) matched by age and educational level. The subjects were all collected serum and detected the serum NFL protein level by enzyme linked immunosorbent assay (ELISA). Results: ①The AD group, aMCI group and CN group had no statistical difference in age, education years and BMI (P>0.05), and the data were comparable. ②AD patients MMSE score was significantly lower than that of aMCI group and CN group [AD group (17.48±7.50), aMCI group (25.56±1.63), CN group (28.60±1.09); F=81.830, P=0.000]. The MoCA score had the most significant difference [AD group (12.04±6.31), aMCI group (19.92±3.17), CN group (27.62±1.16); F=177.187, P=0.000]. ③The NFL protein level of AD group and aMCI group were significantly higher than that of CN group, among which aMCI group was the highest [AD group (4.486±2.463) ng/mL, aMCI group (5.101±2.172) ng/mL and CN group (2.885±1.469) ng/mL, F=15.167, P=0.000]. Spearman correlation analysis found that age, MMSE score, MoCA score, ADL score and CDR score were not correlated with NFL protein levels among the three groups (P>0.05). Conclusion: Serum NFL levels in patients with MCI is the highest, suggesting that serum NFL level may be a peripheral blood biomarker for predicting the early stage of AD.