Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases
Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases
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DOI：
10.1016/j.neuron.2016.05.018
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发表时间：
2016-07-06
期刊：
影响因子：
16.2
通讯作者：
Jucker, Mathias
中科院分区：
文献类型：
--
作者：
Bacioglu, Mehtap;Maia, Luis F.;Jucker, Mathias
目前大多数用于年龄相关神经退行性疾病的疾病改善治疗方法靶向其特征性蛋白质病变（α-突触核蛋白、Tau、A β）。为了监测这些治疗，反映潜在疾病过程的流体生物标志物至关重要。我们在α-突触核蛋白病、tau蛋白病和β-淀粉样变性的小鼠模型中发现CSF和血液中神经丝轻链（NfL）的稳健增加。血液和CSF NfL水平强烈相关，并且NfL增加与脑中相应蛋白质病变的发作和进展一致。实验诱导α-突触核蛋白病变增加CSF和血液NfL水平，而阻断Ab病变减弱NfL增加。因此，我们还发现人α-突触核蛋白病、tau蛋白病和阿尔茨海默病的CSF和血液中NfL增加。我们的研究结果表明，CSF，特别是血液NfL可以作为一个可靠的和容易获得的生物标志物，以监测疾病的进展和治疗反应，在小鼠模型和潜在的人类蛋白质病理性神经退行性疾病。
A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (alpha-synuclein, Tau, A beta). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of alpha-synucleinopathies, tauopathy, and beta-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of alpha-synuclein lesions increased CSF and blood NfL levels, while blocking Ab lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human alpha-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.