Background: Transthyretin amyloidosis due to V30M mutation (ATTR-V30M) is the most frequent hereditary ATTR amyloidosis. Besides neurophysiological measures, there are no biomarkers to detect preclinical disease or monitor disease progression. CSF or plasma neurofilament light chain (pNfL) have recently been considered sensitive biomarkers to quantitate neuro-axonal damage in several disorders of the peripheral and central nervous system.

Objective: Characterise plasma NfL levels in a series of untreated ATTR-V30M patients stratified by clinical severity using a cross-sectional retrospective study design.

Methods: Sixty ATTR-V30M patients and 16 controls from 2 independent cohorts were analysed for pNfL by single-molecule array assay (SIMOA) technique. Disease severity was assessed with Polyneuropathy Disability Score.

Results: pNfL is elevated in ATTR-V30M patients as a function of disease severity in both cohorts. Moreover, pNfL discriminates asymptomatic mutation carriers from early symptomatic patients (AUC = 0.97; p < .001) with high sensitivity (92.3%) and specificity (93.8%). pNfL elevation (>66.9 pg/mL) also discriminates patients with sensory neuropathy from patients with motor neuropathy (AUC = 0.91; p < .01) with a sensitivity of 61.5% and a specificity of 92.3%.

Conclusion: pNfL is an easily accessible biomarker to establish ATTR-V30M disease conversion and to monitor disease progression. pNfL could be used as efficacy measure of disease-oriented therapies in clinical and pre-clinical trials.

背景：由于V30M突变引起的运甲状腺素蛋白淀粉样变性（ATTR-V30M）是最常见的遗传性ATTR淀粉样变性。除了神经生理学措施外，没有生物标志物可检测临床前疾病或监测疾病进展。CSF或血浆神经丝轻链（pNfL）最近被认为是敏感的生物标记，可量化周围和中枢神经系统的几种疾病中的神经轴突损伤。

目的：使用横断面回顾性研究设计，对按临床严重程度分层的一系列未经治疗的ATTR-V30M患者的血浆NfL水平进行特征分析。

方法：采用单分子阵列分析（SIMOA）技术分析了60例ATTR-V30M患者和来自2个独立队列的16例对照的pNfL。用多发性神经病残疾评分评估疾病的严重程度。

结果：两个队列中ATTR-V30M患者的pNfL升高均与疾病严重程度有关。此外，pNfL区分早期症状患者（AUC = 0.97; p  <.001）的无症状突变携带者，具有很高的敏感性（92.3％）和特异性（93.8％）。pNfL升高（> 66.9 pg / mL）还可将感觉神经病患者与运动神经病患者（AUC = 0.91; p  <.01）区分，敏感性为61.5％，特异性为92.3％。

结论： pNfL是易于建立ATTR-V30M疾病转化并监测疾病进展的生物标志物。pNfL可用作临床和临床前试验中针对疾病的疗法的疗效指标。