Mattsson Niklas, Andreasson Ulf, Zetterberg Henrik, Blennow Kaj
Clinical Memory Research Unit, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden2Memory Clinic, Skåne University Hospital, Scania, Sweden3Department of Neurology, Skåne University Hospital, Scania, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden5Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Möndal, Sweden.
JAMA Neurol. 2017 May 1;74(5):557-566. doi: 10.1001/jamaneurol.2016.6117.
Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias.
To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration.
DESIGN, SETTING, AND PARTICIPANTS: In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016.
Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism.
Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally).
Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD.
现有的用于阿尔茨海默病（AD）的脑脊液（CSF）或影像学（tau正电子发射断层扫描）生物标志物具有侵入性或成本高昂。基于标准血液检测结果的生物标志物在研究、药物开发和临床实践中会很有用。血浆神经丝轻链（NFL）最近被提议作为痴呆症神经退行性变的一种基于血液的生物标志物。
测试AD患者血浆NFL浓度是否升高，并与认知功能下降、其他AD生物标志物以及神经退行性变的影像学证据相关。
设计、地点和参与者：在这项前瞻性病例对照研究中，采用超灵敏检测法测量了来自阿尔茨海默病神经影像学计划的193名认知健康对照者、197名轻度认知障碍（MCI）患者和180名AD痴呆患者的血浆NFL浓度。研究日期为2005年9月7日至2012年2月13日。血浆NFL分析于2016年9月进行。
测试血浆NFL与诊断、Aβ病理特征、神经元损伤的CSF生物标志物、认知、脑结构和代谢之间的关联。
在193名认知健康对照者、197名MCI患者和180名AD痴呆患者中，血浆NFL与CSF NFL相关（斯皮尔曼ρ = 0.59，P <.001）。与对照者（平均34.7 ng/L）相比，MCI患者（平均42.8 ng/L）和AD痴呆患者（平均51.0 ng/L）的血浆NFL升高（P <.001），并且对AD痴呆患者与对照者具有较高的诊断准确性（受试者操作特征曲线下面积为0.87，与既定的CSF生物标志物相当）。MCI患者和具有Aβ病理特征的AD痴呆患者的血浆NFL特别高。高血浆NFL与认知功能差和AD相关萎缩（基线和纵向）以及脑代谢减退（纵向）相关。
血浆NFL与AD诊断以及该疾病的认知、生化和影像学特征相关。这一发现意味着血浆NFL作为AD的一种非侵入性生物标志物具有潜在用途。
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