Department of Pediatrics and Neurology, The Children's Hospital of Philadelphia; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
BioMarin Pharmaceutical Inc, 770 Lindaro Street, San Rafael, CA, 94901, USA.
J Neurol. 2020 Sep;267(9):2594-2598. doi: 10.1007/s00415-020-09868-3. Epub 2020 May 8.
The present study evaluates serum neurofilament light chain (NfL) as a biomarker of disease features in Friedreich's ataxia (FRDA).
NfL levels from serum of 117 subjects (85 FRDA patients, 13 carriers, and 19 controls) were assayed and correlated with disease features such as smaller GAA repeat length (GAA1), age, sex, and level of neurological dysfunction.
Mean serum NfL levels were higher in FRDA patients than in carriers or unaffected controls in two independent cohorts of subjects. In longitudinal samples from FRDA patients drawn monthly or 1 year apart, values changed minimally. No difference was noted between carriers and controls. NfL levels correlated positively with age in controls and carriers of similar age, (Rs = 0.72, p < 0.0005), whereas NfL levels inversely correlated with age in FRDA patients (Rs = - 0.63, p < 0.001). NfL levels were not associated with sex or GAA1 length in patients, and linear regression revealed a significant relationship between NfL levels in the cohort with age (coefficient = - 0.36, p < 0.001), but not sex (p = 0.64) or GAA1 (p = 0.13).
Because NfL is elevated in patients, but decreases with age and disease progression, our results suggest that age is the critical determinant of NfL in FRDA (rather than clinical or genetic severity).
本研究评估了血清神经丝轻链（NfL）作为弗里德赖希共济失调（FRDA）疾病特征的生物标志物。
测定了 117 名受试者（85 名 FRDA 患者、13 名携带者和 19 名对照者）血清中的 NfL 水平，并将其与疾病特征相关联，如较小的 GAA 重复长度（GAA1）、年龄、性别和神经功能障碍水平。
在两个独立的受试者队列中，FRDA 患者的平均血清 NfL 水平高于携带者或未受影响的对照组。在 FRDA 患者的纵向样本中，每月或相隔 1 年采集样本，值变化很小。携带者和对照组之间没有差异。NfL 水平与对照组和年龄相似的携带者呈正相关（Rs=0.72，p<0.0005），而与 FRDA 患者呈负相关（Rs=-0.63，p<0.001）。NfL 水平与患者的性别或 GAA1 长度无关，线性回归显示 NfL 水平与队列年龄之间存在显著关系（系数=-0.36，p<0.001），但与性别（p=0.64）或 GAA1 （p=0.13）无关。
由于患者的 NfL 水平升高，而随着年龄和疾病的进展而降低，我们的结果表明年龄是 FRDA 中 NfL 的关键决定因素（而不是临床或遗传严重程度）。
