Table_4_Neurofilament light as a biomarker for motor decline in Parkinson’s disease.xlsx

ObjectivesThe aim of this study was to determine whether neurofifilament light (NfL) could reflect motor decline and compare the predictive values of cerebrospinal fluid (CSF) and serum NfL in individuals with PD.
MethodsCSF/serum samples were collected from patients with PD and healthy controls (HCs) with motor assessments at baseline and after three years of follow-up from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression models and linear mixed-effects models were used to investigate the associations of motor assessments with baseline and longitudinal CSF/serum NfL. Associations between the change rates of motor assessments and CSF/serum NfL were further investigated via multiple linear regression models. Mediating effect analysis was used to research whether CSF alpha-synuclein (α-syn) acts as the mediator between NfL and motor assessments.
ResultsWe found patients with PD had higher baseline CSF/serum NfL levels than HCs. Both baseline CSF/serum NfLs and their change rates predicted measurable motor decline in PD assessed by different motor scores. Baseline serum NfL and its rate of change were strongly associated with CSF NfL levels in patients with PD (P < 0.001). Besides, there were also significant differences in CSF/serum NfL levels and predicted values of motor decline between men and women with PD. Mediating effect analysis showed CSF α-syn mediated the effect of CSF NfL on total Unified Parkinson’s Disease Rating Scale (UPDRS) scores and UPDRSIII with 30.6 and 20.2% mediation, respectively.
ConclusionOur results indicated that NfL, especially serum NfL concentration, could serve as an easily accessible biomarker to monitor the severity and progression of motor decline in individuals with PD, especially in men with PD. Besides, CSF α-syn acts as a mediator between NfL and motor progression.

研究目的：本研究旨在明确神经丝轻链蛋白（neurofilament light, NfL）是否可反映运动功能衰退，并比较脑脊液（cerebrospinal fluid, CSF）与血清NfL对帕金森病（Parkinson’s Disease, PD）患者的预测价值。
研究方法：本研究样本来自帕金森病进展标志物倡议（Parkinson’s Progression Markers Initiative, PPMI）队列，纳入PD患者与健康对照（healthy controls, HCs），在基线时及3年随访后对受试者进行运动功能评估，并采集其CSF与血清样本。采用多重线性回归模型与线性混合效应模型，探究运动功能评估结果与基线及纵向CSF/血清NfL水平的关联。进一步通过多重线性回归模型，分析运动功能评估结果的变化速率与CSF/血清NfL的相关性。此外，采用中介效应分析，探究脑脊液α-突触核蛋白（alpha-synuclein, α-syn）是否在NfL与运动功能评估结果之间发挥中介作用。
研究结果：本研究发现，PD患者的基线CSF与血清NfL水平均高于健康对照。基线CSF、血清NfL水平及其变化速率，均可通过不同运动评分有效预测PD患者的运动功能衰退情况。PD患者的基线血清NfL水平及其变化速率，与CSF NfL水平呈强相关（P < 0.001）。此外，PD男性与女性患者的CSF、血清NfL水平及运动功能衰退预测值存在显著差异。中介效应分析结果显示，CSF α-syn分别介导了CSF NfL对统一帕金森病评定量表（Unified Parkinson’s Disease Rating Scale, UPDRS）总分及UPDRSIII评分的影响，中介效应占比分别为30.6%与20.2%。
研究结论：本研究结果表明，NfL，尤其是血清NfL浓度，可作为一种易于获取的生物标志物，用于监测PD患者运动功能衰退的严重程度与进展情况，尤其适用于男性PD患者。此外，CSF α-syn在NfL与运动功能进展之间发挥中介作用。