Neurofilament light chain in spinal fluid and plasma in multiple system atrophy: a prospective, longitudinal biomarker study.

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY
Clinical Autonomic Research Pub Date : 2023-12-01 Epub Date: 2023-08-21 DOI:10.1007/s10286-023-00974-6
Wolfgang Singer, Ann M Schmeichel, David M Sletten, Tonette L Gehrking, Jade A Gehrking, Jorge Trejo-Lopez, Mariana D Suarez, Jennifer K Anderson, Pamela H Bass, Timothy G Lesnick, Phillip A Low
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Abstract

Purpose: There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression.

Methods: Well-characterized patients with early MSA (n = 32), Parkinson's disease (PD; n = 21), and matched controls (CON; n = 15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high-sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression.

Results: Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r = 0.99), while correlation between NfL-c and -p was only moderate (r = 0.66). NfL was significantly higher in MSA compared with CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity.

Conclusions: These findings confirm NfL-c as a faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression.

Abstract Image

多系统萎缩症患者脊髓液和血浆中的神经丝轻链:一项前瞻性纵向生物标记物研究。
目的:多系统萎缩症(MSA)患者亟需可靠的诊断生物标志物以及疾病进展的替代标志物。据报道,神经丝蛋白轻链(NfL)有可能满足这些需求。因此,我们试图探索血浆(NfL-p)与脑脊液(NfL-c)中的NfL作为MSA诊断标志物的价值,并评估NfL-p和NfL-c作为临床疾病进展标志物的价值:一项关于突触核蛋白病的前瞻性纵向研究招募了特征明确的早期MSA患者(32人)、帕金森病患者(21人)和匹配对照组(15人),并每年进行连续评估。使用高灵敏度免疫测定法测定NfL,并按疾病类别和与疾病进展临床指标的关系对结果进行评估:不同免疫测定平台对 NfL-c 的测量结果具有很高的重现性(Pearson,r = 0.99),而 NfL-c 和 -p 之间的相关性仅为中等(r = 0.66)。与CON和PD相比,MSA的NfL明显更高;NfL-c的分离基本上是完美的,但NfL-p存在重叠,尤其是与PD。随着时间的推移,疾病严重程度的临床指标逐渐增加,但在连续测量中,受试者的 NfL-c 和 -p 仍保持稳定的升高水平。NfL和基线NfL的变化均与疾病严重程度临床指标的变化无明显关联:这些研究结果证实,NfL-c 是 MSA 的可靠诊断标志物,而 NfL-p 的诊断价值则不那么可靠。MSA患者NfL的明显升高随着时间的推移非常稳定,并不能预测临床疾病的进展。
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来源期刊
Clinical Autonomic Research
Clinical Autonomic Research 医学-临床神经学
CiteScore
7.40
自引率
6.90%
发文量
65
审稿时长
>12 weeks
期刊介绍: Clinical Autonomic Research aims to draw together and disseminate research work from various disciplines and specialties dealing with clinical problems resulting from autonomic dysfunction. Areas to be covered include: cardiovascular system, neurology, diabetes, endocrinology, urology, pain disorders, ophthalmology, gastroenterology, toxicology and clinical pharmacology, skin infectious diseases, renal disease. This journal is an essential source of new information for everyone working in areas involving the autonomic nervous system. A major feature of Clinical Autonomic Research is its speed of publication coupled with the highest refereeing standards.
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