Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal.
Department of Informatics Engineering, Centre for Informatics and Systems, University of Coimbra, Coimbra, Portugal.
Eur J Neurol. 2022 Jan;29(1):36-46. doi: 10.1111/ene.15058. Epub 2021 Sep 3.
Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD.
CSF and serum NfL, as well as conventional CSF Alzheimer's disease (AD) biomarkers (Aβ42, t-Tau, p-Tau181), were determined in 63 FTD patients (30 sporadic-FTD, 20 with progranulin (GRN) mutations [FTD-GRN], 13 with chromosome 9 open reading frame 72 [C9orf72] expansions [C9orf72-FTD]), 37 AD patients, and 31 neurologic controls. Serum NfL was also quantified in 37 healthy individuals. Correlations between baseline CSF and serum NfL levels, standardized neuropsychological tests, and the rate of cognitive decline in FTD patients were assessed.
CSF and serum NfL presented with significantly higher levels in FTD than in AD patients and both control groups. Within FTD subtypes, genetic cases, and particularly FTD-GRN, had higher CSF and serum NfL levels. Significant correlations between NfL levels and overall cognitive function, abstract reasoning (CSF and serum), executive functions, memory, and language (serum) were found. A relationship between increased baseline CSF and serum NfL and a decay in cognitive performance over time was also observed.
Our findings highlight the potential of serum NfL as a useful surrogate end point of disease severity in upcoming targeted treatments.
神经丝轻链（NfL）最近被提议作为额颞叶痴呆（FTD）的一种有前途的生物标志物。我们研究了脑脊液（CSF）和血清 NfL 与详细的神经心理学数据以及散发性和家族性 FTD 队列中认知能力下降的相关性。
在 63 名 FTD 患者（30 名散发性-FTD、20 名颗粒蛋白前体（GRN）突变[FTD-GRN]、13 名 9 号染色体开放阅读框 72 [C9orf72] 扩增[C9orf72-FTD]）、37 名 AD 患者和 31 名神经科对照组中，测定了 CSF 和血清 NfL 以及常规 CSF 阿尔茨海默病（AD）生物标志物（Aβ42、t-Tau、p-Tau181）。还在 37 名健康个体中定量了血清 NfL。评估了 FTD 患者基线 CSF 和血清 NfL 水平、标准化神经心理学测试和认知衰退率之间的相关性。
与 AD 患者和两个对照组相比，CSF 和血清 NfL 在 FTD 中表现出显著更高的水平。在 FTD 亚型中，遗传病例，特别是 FTD-GRN，具有更高的 CSF 和血清 NfL 水平。发现 NfL 水平与整体认知功能、抽象推理（CSF 和血清）、执行功能、记忆和语言（血清）之间存在显著相关性。还观察到基线 CSF 和血清 NfL 升高与认知表现随时间下降之间的关系。
我们的研究结果强调了血清 NfL 作为未来靶向治疗中疾病严重程度的有用替代终点的潜力。
