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不同临床应用情境下的血液神经丝轻链蛋白在神经退行性疾病谱中的应用。

Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases.

机构信息

Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Centre National de Référence des Démences Rares ou Précoces, IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France.

出版信息

Mol Neurobiol. 2020 Nov;57(11):4667-4691. doi: 10.1007/s12035-020-02035-9. Epub 2020 Aug 9.

Abstract

One of the most pressing challenges in the clinical research of neurodegenerative diseases (NDDs) is the validation and standardization of pathophysiological biomarkers for different contexts of use (CoUs), such as early detection, diagnosis, prognosis, and prediction of treatment response. Neurofilament light chain (NFL) concentration is a particularly promising candidate, an indicator of axonal degeneration, which can be analyzed in peripheral blood with advanced ultrasensitive methods. Serum/plasma NFL concentration is closely correlated with cerebrospinal fluid NFL and directly reflects neurodegeneration within the central nervous system. Here, we provide an update on the feasible CoU of blood NFL in NDDs and translate recent findings to potentially valuable clinical practice applications. As NFL is not a disease-specific biomarker, however, blood NFL is an easily accessible biomarker with promising different clinical applications for several NDDs: (1) early detection and diagnosis (i.e., amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, atypical parkinsonisms, sporadic late-onset ataxias), (2) prognosis (Huntington's disease and Parkinson's disease), and (3) prediction of time to symptom onset (presymptomatic mutation carriers in genetic Alzheimer's disease and spinocerebellar ataxia type 3).

摘要

神经退行性疾病(NDD)临床研究中最紧迫的挑战之一是为不同的应用场景(CoU)验证和标准化生理病理学生物标志物,例如早期检测、诊断、预后和治疗反应预测。神经丝轻链(NFL)浓度是一个非常有前途的候选物,是轴突退化的指标,可以通过先进的超灵敏方法在周围血液中进行分析。血清/血浆 NFL 浓度与脑脊液 NFL 密切相关,直接反映中枢神经系统内的神经退行性变。在这里,我们提供了血液 NFL 在 NDD 中可行的 CoU 的最新信息,并将最近的发现转化为潜在有价值的临床实践应用。然而,由于 NFL 不是一种特定于疾病的生物标志物,因此血液 NFL 是一种易于获取的生物标志物,在几种 NDD 中有多种有前途的临床应用:(1)早期检测和诊断(即肌萎缩侧索硬化症、克雅氏病、非典型帕金森病、散发性晚发性共济失调);(2)预后(亨廷顿病和帕金森病);以及(3)症状出现时间的预测(遗传性阿尔茨海默病和脊髓小脑共济失调 3 型的无症状突变携带者)。

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