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Brain Science Advances 2019, 5(2): 94-105 https://doi.org/10.26599/BSA.2019.9050011
Research Article | Open Access | Issue | Published: 17 January 2020

Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease

Show Author's Information Ya-Nan Ou1,  Hao Hu1,  Zuo-Teng Wang2,  Wei Xu1,  Lan Tan1( ),  Jin-Tai Yu3( )
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong, China
College of Medicine and Pharmaceutics, Ocean University of China, Qingdao 266100, Shandong, China
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200433, China
Keywords:
Alzheimer’s disease, plasma neurofilament light (NFL), longitudinal, neurodegeneration
Cite this article:
Ou Y-N, Hu H, Wang Z-T, et al. Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease. Brain Science Advances, 2019, 5(2): 94-105. https://doi.org/10.26599/BSA.2019.9050011
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Abstract Full text About this article
Objective:

To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD).

Methods:

A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion.

Results:

Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally (p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time (p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model.

Conclusion:

Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.


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Abstract
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About this article

Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease

Show Author's information Ya-Nan Ou1, Hao Hu1, Zuo-Teng Wang2, Wei Xu1, Lan Tan1( ), Jin-Tai Yu3( )
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong, China
College of Medicine and Pharmaceutics, Ocean University of China, Qingdao 266100, Shandong, China
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200433, China

Abstract

Objective:

To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD).

Methods:

A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion.

Results:

Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally (p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time (p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model.

Conclusion:

Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.

Keywords: Alzheimer’s disease, plasma neurofilament light (NFL), longitudinal, neurodegeneration

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Publication history
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Acknowledgements
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Publication history

Received: 01 May 2019
Revised: 24 May 2019
Accepted: 14 June 2019
Published: 17 January 2020
Issue date: June 2019

Copyright

© The authors 2019

Acknowledgements

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

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