Research Paper Volume 11, Issue 17 pp 6904—6914

Neurofilament light chain plasma concentration predicts neurodegeneration and clinical progression in nondemented elderly adults

Hao Hu1, , Ke-Liang Chen2, , Ya-Nan Ou1, , Xi-Peng Cao3, , Shi-Dong Chen2, , Mei Cui2, , Qiang Dong2, , Lan Tan1, , Jin-Tai Yu2, , Alzheimer’s Disease Neuroimaging Initiative *, ,

  • 1 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
  • 2 Department of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  • 3 Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
* Data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database ( As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at:

Received: July 6, 2019       Accepted: August 13, 2019       Published: September 12, 2019
How to Cite

Copyright © 2019 Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Previous studies demonstrated that plasma neurofilament light chain (NFL) played important predictive roles in disease progression and neurodegeneration in the preclinical phase of familial Alzheimer’s disease (AD). However, whether plasma NFL has the same predictive roles in sporadic AD is still unclear. In this study, 243 cognitively normal (CN) participants from the ADNI database were divided into two subgroups (CN- and CN+) according to CSF Aβ or AV45-PET. Associations of baseline plasma NFL concentrations or rate of change in plasma NFL with longitudinal data on other biomarkers were tested by multivariate linear mixed effects models (LMEMs). Results showed that plasma NFL concentration and its rate of change were already abnormally high in the preclinical phase of AD. Plasma NFL was associated with three core AD-related biomarkers in preclinical phase. Baseline plasma NFL, but not its rate of change, played predictive roles in both cognitive decline (β = -0.0349, p = 0.0274) and hippocampal atrophy (β = -0.0351, p = 0.0088), especially for preclinical AD participants. In summary, these results indicated that baseline plasma NFL, but not its rate of change, may be a valuable noninvasive tool to assess neurodegeneration and predict longitudinal disease progression in preclinical AD individuals.


AD: Alzheimer disease; ADNI: Alzheimer’s Disease Neuroimaging Initiative; APOEε4: apolipoprotein Eε4 genotype; Aβ: β-amyloid; CDR: Clinical Dementia Rating; CN: cognitively normal; CSF: cerebrospinal fluid; CSF p-tau: phosphorylated tau protein in cerebrospinal fluid; CSF t-tau: total of tau protein in cerebrospinal fluid; FDG-PET: F18-fluorodeoxyglucose positron emission tomography; FTD: frontotemporal dementia; LMEM: linear mixed-effects model; MCI: mild cognitive impairment; MRI: magnetic resonance imaging; MMSE: mini-mental state examination; NFL: Neurofilament light; Ng: neurogranin; NIA-AA: National Institute of Aging-Alzheimer’s Association; PSP: progressive supranuclear palsy; ROI: regions of interest; SD: standard deviation.