Singer Wolfgang, Schmeichel Ann M, Sletten David M, Gehrking Tonette L, Gehrking Jade A, Trejo-Lopez Jorge, Suarez Mariana D, Anderson Jennifer K, Bass Pamela H, Lesnick Timothy G, Low Phillip A
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Res Sq. 2023 Aug 1:rs.3.rs-3201386. doi: 10.21203/rs.3.rs-3201386/v1.
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 CSF (NfL-c) as 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 to 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 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.
在多系统萎缩（MSA）中，迫切需要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，神经丝轻链（NfL）可能满足这些需求。因此，我们试图探讨血浆中NfL（NfL-p）与脑脊液中NfL（NfL-c）相比作为MSA诊断标志物的价值，并评估NfL-p和NfL-c作为临床疾病进展的标志物。方法：对特征明确的早期MSA患者（n = 32）、帕金森病（PD，n = 21）患者和匹配的对照组（CON，n = 15）进行一项关于突触核蛋白病的前瞻性纵向研究，每年进行系列评估。使用高灵敏度免疫测定法测量NfL，并根据疾病类别以及与疾病进展临床指标的关系评估结果。结果：NfL-c在不同免疫测定平台上的测量结果具有高度可重复性（Pearson相关系数，r = 0.99），而NfL-c与NfL-p之间的相关性仅为中等（r = 0.66）。与CON和PD相比，MSA患者的NfL显著更高；NfL-c的区分基本完美，但NfL-p存在重叠，特别是与PD有重叠。虽然疾病严重程度的临床指标随时间逐渐增加，但在连续测量中，受试者体内的NfL-c和NfL-p保持在稳定的升高水平。NfL的变化和基线NfL均与疾病严重程度的临床标志物变化无显著相关性。结论：这些发现证实NfL-c是MSA可靠的诊断标志物，而NfL-p的诊断价值较弱。发现MSA中NfL的显著升高随时间非常稳定，且不能预测临床疾病进展。
