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Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals

, ; Benedet, Andréa L.; Ashton, Nicholas J.; Pascoal, Tharick A.; Leuzy, Antoine LU ; Mathotaarachchi, Sulantha; Kang, Min S.; Therriault, Joseph; Savard, Melissa and Chamoun, Mira, et al. (2019) In Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring 11. p.679-689
Abstract

Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results:... (More)

Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [18F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [18F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.

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keywords
Alzheimer's disease, Biomarkers, Blood, Hypometabolism, Longitudinal, Neurodegeneration, Neurofilament light, PET, [F]FDG
in
Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
volume
11
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:85072700126
ISSN
2352-8729
DOI
10.1016/j.dadm.2019.08.002
language
English
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yes
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58af0059-756c-48eb-9ae0-ab1a50d06467
date added to LUP
2019-10-09 14:18:22
date last changed
2019-10-09 14:18:22
@article{58af0059-756c-48eb-9ae0-ab1a50d06467,
  abstract     = {<p>Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [<sup>18</sup>F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [<sup>18</sup>F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [<sup>18</sup>F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.</p>},
  author       = {,  and Benedet, Andréa L. and Ashton, Nicholas J. and Pascoal, Tharick A. and Leuzy, Antoine and Mathotaarachchi, Sulantha and Kang, Min S. and Therriault, Joseph and Savard, Melissa and Chamoun, Mira and Schöll, Michael and Zimmer, Eduardo R. and Gauthier, Serge and Labbe, Aurélie and Zetterberg, Henrik and Blennow, Kaj and Neto, Pedro R.},
  issn         = {2352-8729},
  keyword      = {Alzheimer's disease,Biomarkers,Blood,Hypometabolism,Longitudinal,Neurodegeneration,Neurofilament light,PET,[F]FDG},
  language     = {eng},
  pages        = {679--689},
  publisher    = {Elsevier},
  series       = {Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring},
  title        = {Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals},
  url          = {http://dx.doi.org/10.1016/j.dadm.2019.08.002},
  volume       = {11},
  year         = {2019},
}