IMR Press / JIN / Volume 20 / Issue 4 / DOI: 10.31083/j.jin2004088
Open Access Original Research
Neurofilament light as a biomarker of axonal degeneration in patients with mild cognitive impairment and Alzheimer’s disease
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1 Department of Radiology, Chongqing Red Cross Hospital (Jiangbei District People’s Hospital), 400020 Chongqing, China
2 The McGill University Research Centre for Studies in Aging, McGill University, Montreal, QC H2L, Canada
3 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
4 Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, 264000 Shandong, China

§Alzheimer's Disease Neuroimaging Initiative, Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

J. Integr. Neurosci. 2021, 20(4), 861–870; https://doi.org/10.31083/j.jin2004088
Submitted: 17 June 2021 | Revised: 12 October 2021 | Accepted: 26 October 2021 | Published: 30 December 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Cerebrospinal fluid neurofilament light and plasma neurofilament light concentrations are elevated in patients with mild cognitive impairment and Alzheimer’s disease. We investigated the clinical relevance of increased neurofilament light concentrations in mild cognitive impairment and Alzheimer’s disease patients. In this study, 244 subjects were divided into cognitively normal control (n = 67), stable mild cognitive impairment (n = 52), progressive mild cognitive impairment (n = 68), and Alzheimer’s disease (n = 57). Linear regression examined the relationships between neurofilament light levels in cerebrospinal fluid or plasma and the diagnostic group. The relationships between neurofilament light and other biomarkers were assessed by Spearman correlation. Linear mixed-effects models were used to test cerebrospinal fluid and plasma neurofilament light as predictors of Alzheimer’s disease characteristics, including cognition, cortical glucose metabolism, and brain structure. Cerebrospinal fluid and plasma neurofilament light levels were significantly elevated in Alzheimer’s disease. Still, the correlations between neurofilament light and other cerebrospinal fluid biomarkers within the diagnostic groups were often not statistically significant. In addition, the diagnostic accuracy of cerebrospinal fluid and plasma neurofilament light for progressive mild cognitive impairment and Alzheimer’s disease was almost the same as that of cerebrospinal fluid total tau (T-tau). It is phosphorylated tau (P-tau) and high cerebrospinal fluid. Neurofilament light predicted conversion from mild cognitive impairment to Alzheimer’s disease. A high neurofilament light is related to poor cognition, low cerebral metabolism, hippocampal atrophy, and ventricular enlargement caused by Alzheimer’s disease. Our work further identifies cerebrospinal fluid neurofilament light and plasma neurofilament light as biomarkers of axonal degeneration in patients with mild cognitive impairment and Alzheimer’s disease.

Keywords
Neurofilament light
Alzheimer's disease
Mild cognitive impairment
Cerebrospinal fluid
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