Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: NfL levels correlated with examination scores (CMTNS, NIS and MRC; all p < .01) and increased with disease severity (PND and FAP; all p < .05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all p < .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 (r = 0.64, p = .008).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: NfL levels correlated with examination scores (CMTNS, NIS and MRC; all p < .01) and increased with disease severity (PND and FAP; all p < .05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all p < .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 (r = 0.64, p = .008).
UNASSIGNED: 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.
摘要：
■神经丝轻链（NfL）已成为遗传性转甲状腺素蛋白淀粉样多发性神经病（ATTRv-PN）的敏感生物标志物。我们假设NfL可以识别基因携带者转化为有症状的疾病，并指导治疗方法。
■在59名有症状和有症状的ATTR变异携带者中纵向（2015-2022年）测量了血清NfL浓度。NFL和人口统计学之间的相关性，进行生物化学和分期评分以及治疗前后的纵向变化，以及无症状和有症状的队列。进行接收器操作分析以确定截止值。
■NfL水平与考试成绩相关(CMTNS，NIS和MRC；所有p<0.01），并随疾病严重程度增加（PND和FAP；所有p<0.05）。有症状和感觉运动转换器的NfL较高，与时间无关的无症状或感觉转换器（所有p<.001）。根据NfL浓度>64.5pg/ml（灵敏度=91.9%，特异性=88.5%)，而无症状患者只能通过NfL浓度>88.9pg/ml（灵敏度=62.9%，特异性=96.2%)然而，在6个月内增加17%的NfL可以区分无症状和感觉或感觉运动转换器(灵敏度=88.9%，特异性=80.0%)。NfL随治疗降低36%/年，与TTR抑制相关（r=0.64，p=.008）。
■该数据验证了使用血清NfL来识别ATTRv-PN中转化为有症状的疾病。NfL水平可以指导疾病进展和对治疗的反应的评估。
■在59名有症状和有症状的ATTR变异携带者中纵向（2015-2022年）测量了血清NfL浓度。NFL和人口统计学之间的相关性，进行生物化学和分期评分以及治疗前后的纵向变化，以及无症状和有症状的队列。进行接收器操作分析以确定截止值。
■NfL水平与考试成绩相关(CMTNS，NIS和MRC；所有p<0.01），并随疾病严重程度增加（PND和FAP；所有p<0.05）。有症状和感觉运动转换器的NfL较高，与时间无关的无症状或感觉转换器（所有p<.001）。根据NfL浓度>64.5pg/ml（灵敏度=91.9%，特异性=88.5%)，而无症状患者只能通过NfL浓度>88.9pg/ml（灵敏度=62.9%，特异性=96.2%)然而，在6个月内增加17%的NfL可以区分无症状和感觉或感觉运动转换器(灵敏度=88.9%，特异性=80.0%)。NfL随治疗降低36%/年，与TTR抑制相关（r=0.64，p=.008）。
■该数据验证了使用血清NfL来识别ATTRv-PN中转化为有症状的疾病。NfL水平可以指导疾病进展和对治疗的反应的评估。
