Blood NfL A biomarker for disease severity and progression in Parkinson disease
Blood NfL A biomarker for disease severity and progression in Parkinson disease
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DOI：
10.1212/wnl.0000000000008088
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发表时间：
2019-09-10
期刊：
影响因子：
9.9
通讯作者：
Chiu, Ming-Jang
中科院分区：
文献类型：
--
作者：
Lin, Chin-Hsien;Li, Cheng-Hsuan;Chiu, Ming-Jang
目的探讨血浆神经丝轻链(NFL)水平与帕金森病(PD)患者运动和认知功能进展的关系。方法前瞻性随访178例帕金森病患者，其中帕金森病116例，多系统萎缩22例，健康对照组40例。采用电化学发光免疫分析法检测血浆NFL水平。帕金森病患者在基线时和平均3年的随访间隔中接受运动和认知评估。采用统一帕金森病评定量表第三部分运动评分和简易智力状态检查评分评定患者的运动和认知功能。结果帕金森病患者血浆神经营养因子水平显著高于帕金森病组和健康对照组(分别为35.8±6.2、17.6±2.8和10.6±2.3pg/m L，p<；0.001)。在PD组中，晚期Hoehn-Yahr期患者和痴呆症患者的NFL水平显著升高(p<；0.001)。NFL水平与UPDRS第三部分得分呈正相关(r=0.4295%可信区间0.46-0.56，p<；0.001)。经过平均3.4年+/-1.2年的随访，根据年龄、性别、病程和基线运动或认知状态进行校正的COX回归分析显示，基线水平越高，运动或认知进展的风险越高(分别为p=0.029和p=0.015)。结论血浆神经营养因子水平与疾病严重程度和疾病进展相关，包括运动和认知功能。证据分类本研究提供了Ⅲ类证据，表明血浆神经营养因子水平区分了帕金森病和多发性硬化症，是帕金森病进展的替代生物标志物。
ObjectiveTo examine whether plasma neurofilament light chain (NfL) levels were associated with motor and cognitive progression in Parkinson disease (PD).MethodsThis prospective follow-up study enrolled 178 participants, including 116 with PD, 22 with multiple system atrophy (MSA), and 40 healthy controls. We measured plasma NfL levels with electrochemiluminescence immunoassay. Patients with PD received evaluations of motor and cognition at baseline and at a mean follow-up interval of 3 years. Changes in the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score and Mini-Mental State Examination score were used to assess motor and cognition progression.ResultsPlasma NfL levels were significantly higher in the MSA group than in the PD and healthy groups (35.8 +/- 6.2, 17.6 +/- 2.8, and 10.6 +/- 2.3 pg/mL, respectively, p < 0.001). In the PD group, NfL levels were significantly elevated in patients with advanced Hoehn-Yahr stage and patients with dementia (p < 0.001). NfL levels were modestly correlated with UPDRS part III scores (r = 0.42, 95% confidence interval 0.46-0.56, p < 0.001). After a mean follow-up of 3.4 +/- 1.2 years, a Cox regression analysis adjusted for age, sex, disease duration, and baseline motor or cognitive status showed that higher baseline NfL levels were associated with higher risks for either motor or cognition progression (p = 0.029 and p = 0.015, respectively).ConclusionsPlasma NfL levels correlated with disease severity and progression in terms of both motor and cognitive functions in PD.Classification of evidenceThis study provides Class III evidence that plasma NfL level distinguishes PD from MSA and is a surrogate biomarker for PD progression.