Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Nat Commun. 2021 Jun 7;12(1):3400. doi: 10.1038/s41467-021-23620-z.
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
脑脊液神经丝轻链（NfL）增加是神经退行性变的公认生物标志物，也可以在血液中进行评估。在这里，我们研究了来自两个多中心队列（伦敦国王学院（n=805）和瑞典 BioFINDER 研究（n=1464））的 13 种神经退行性疾病、唐氏综合征、抑郁症和认知正常对照者的血浆 NfL 作为神经退行性变的标志物。所有皮质神经退行性疾病、肌萎缩侧索硬化症和非典型帕金森病均显著增加了血浆 NfL。我们证明，血浆 NfL 在识别帕金森病患者中的非典型帕金森病、唐氏综合征患者中的痴呆、精神障碍患者中的痴呆以及认知障碍患者中的额颞叶痴呆方面具有临床意义。基于数据的截止值突出了与发病年龄较早的疾病相关的年龄相关临床截止值的重要性。最后，在所有与年龄相关的截止值下，当用于指示无潜在神经退行性变时，血浆 NfL 的假阳性率最低，性能最佳。
