Brain and Mind Centre, Faculty of Medicine and Health, Translational Research Collective University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia.
Centre for Neuromuscular disease, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Amyloid. 2024 Jun;31(2):95-104. doi: 10.1080/13506129.2024.2313218. Epub 2024 Feb 13.
Neurofilament light chain (NfL) has emerged as a sensitive biomarker in hereditary transthyretin amyloid polyneuropathy (ATTRv-PN). We hypothesise that NfL can identify conversion of gene carriers to symptomatic disease, and guide treatment approaches.
Serum NfL concentration was measured longitudinally (2015-2022) in 59 presymptomatic and symptomatic ATTR variant carriers. Correlations between NfL and demographics, biochemistry and staging scores were performed as well as longitudinal changes pre- and post-treatment, and in asymptomatic and symptomatic cohorts. Receiver-operating analyses were performed to determine cut-off values.
NfL levels correlated with examination scores (CMTNS, NIS and MRC; all < .01) and increased with disease severity (PND and FAP; all < .05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all < .001). Symptomatic or sensorimotor converters were discriminated from asymptomatic patients by NfL concentrations >64.5 pg/ml (sensitivity= 91.9%, specificity = 88.5%), whereas asymptomatic patients could only be discriminated from sensory or sensorimotor converters or symptomatic individuals by a NfL concentration >88.9 pg/ml (sensitivity = 62.9%, specificity = 96.2%) However, an NfL increment of 17% over 6 months could discriminate asymptomatic from sensory or sensorimotor converters (sensitivity = 88.9%, specificity = 80.0%). NfL reduced with treatment by 36%/year and correlated with TTR suppression ( = 0.64, = .008).
This data validates the use of serum NfL to identify conversion to symptomatic disease in ATTRv-PN. NfL levels can guide assessment of disease progression and response to therapies.
神经丝轻链（NfL）已成为遗传性转甲状腺素蛋白淀粉样多神经病（ATTRv-PN）的一种敏感生物标志物。我们假设 NfL 可以识别基因携带者向有症状疾病的转化，并指导治疗方法。
在 59 名无症状和有症状的 ATTR 变体携带者中，纵向测量（2015-2022 年）血清 NfL 浓度。对 NfL 与人口统计学、生物化学和分期评分之间的相关性进行了分析，以及治疗前后、无症状和有症状队列中的纵向变化。进行了接收器操作分析以确定截断值。
NfL 水平与检查评分（CMTNS、NIS 和 MRC；均 < .01）相关，并随疾病严重程度增加（PND 和 FAP；均 < .05）。与无症状或感觉性转化者相比，有症状或感觉运动性转化者的 NfL 水平更高，无论时间如何（均 < .001）。NfL 浓度>64.5 pg/ml 可将有症状或感觉运动性转化者与无症状患者区分开来（敏感性=91.9%，特异性=88.5%），而无症状患者只能通过 NfL 浓度>88.9 pg/ml 与感觉性或感觉运动性转化者或有症状个体区分开来（敏感性=62.9%，特异性=96.2%）。然而，6 个月内 NfL 增加 17%可将无症状与感觉性或感觉运动性转化者区分开来（敏感性=88.9%，特异性=80.0%）。NfL 每年减少 36%，与 TTR 抑制相关（ = 0.64， = .008）。
这些数据验证了血清 NfL 用于识别 ATTRv-PN 向有症状疾病的转化。NfL 水平可以指导疾病进展和对治疗的反应评估。
