Plasma neurofilament light chain predicts progression in progressive supranuclear palsy.
Plasma neurofilament light chain predicts progression in progressive supranuclear palsy.
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DOI：
10.1002/acn3.290
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发表时间：
2016-03
影响因子：
5.3
通讯作者：
Boxer AL
中科院分区：
文献类型：
--
作者：
Rojas JC;Karydas A;Bang J;Tsai RM;Blennow K;Liman V;Kramer JH;Rosen H;Miller BL;Zetterberg H;Boxer AL
神经退行性疾病的血液生物标志物可以改善诊断和治疗开发。进行性核上性麻痹（PSP）患者的脑脊液（CSF）中神经丝轻链（NfL）升高，这是轴突损伤的标志物。本研究的目的是确定血浆NfL在PSP患者中的诊断和预后价值。在15例PSP患者和12例健康对照的试点队列以及147例PSP患者的验证队列中，采用基于超灵敏数字免疫测定技术的基线和1年随访时测量血浆NfL。混合线性模型测试了血浆NfL预测神经、认知和功能下降以及脑萎缩的能力。PSP患者的基线平均血浆NfL水平升高（31 ± 4 pg/mL，与对照组相比，17.5 ± 1 pg/mL，P < 0.05），并且这种差异在随访时持续存在。20 pg/mL的临界值与PSP的诊断相关，灵敏度为0.80，特异性为0.83（阳性似然比= 4.7，阴性似然比为0.24）。NfL水平较高的患者在1年内有更严重的神经系统（PSPRS，−36.9% vs. − 28.9%，P = 0.04），功能（SEADL，−38.2% vs. − 20%，P = 0.03）和神经心理（RBANS，−23.9% vs. − 12.3%，P = 0.01）恶化。较高的基线NfL预测较大的全脑和上级小脑脚体积损失。血浆和CSF NfL呈显著相关（r = 0.74，P = 0.002）。血浆NfL在PSP中升高，并且可以作为生物标志物用于辅助临床诊断和监测临床试验中对神经退行性过程的药效学作用。
Blood‐based biomarkers for neurodegenerative conditions could improve diagnosis and treatment development. Neurofilament light chain (NfL), a marker of axonal injury, is elevated in cerebrospinal fluid (CSF) of patients with progressive supranuclear palsy (PSP). The goal of this study was to determine the diagnostic and prognostic value of plasma NfL in patients with PSP. Plasma NfL was measured with ultrasensitive digital immunoassay‐based technology at baseline and 1‐year follow‐up in a pilot cohort of 15 PSP patients and 12 healthy controls, and a validation cohort of 147 PSP patients. Mixed linear models tested the ability of plasma NfL to predict neurological, cognitive and functional decline, and brain atrophy. Baseline mean plasma NfL levels were elevated in PSP patients (31 ± 4 pg/mL, vs. control, 17.5 ± 1 pg/mL, P < 0.05) and this difference persisted at follow‐up. A cutoff value of 20 pg/mL related to the diagnosis of PSP with a sensitivity of 0.80 and specificity of 0.83 (positive likelihood ratio = 4.7 and a negative likelihood radio of 0.24). Patients with higher NfL levels had more severe neurological (PSPRS, −36.9% vs. −28.9%, P = 0.04), functional (SEADL, −38.2% vs. −20%, P = 0.03), and neuropsychological (RBANS, −23.9% vs. −12.3%, P = 001) deterioration over 1 year. Higher baseline NfL predicted greater whole‐brain and superior cerebellar peduncle volume loss. Plasma and CSF NfL were significantly correlated (r = 0.74, P = 0.002). Plasma NfL is elevated in PSP and could be of value as a biomarker both to assist clinical diagnosis and to monitor pharmacodynamic effects on the neurodegenerative process in clinical trials.