Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease.
Alzheimer's disease
Blood-based biomarkers
Neurodegeneration
Neurofilament
Neuroimaging
White matter
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
24
02
2020
revised:
03
05
2020
accepted:
04
06
2020
pubmed:
12
6
2020
medline:
28
7
2021
entrez:
12
6
2020
Statut:
ppublish
Résumé
Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.
Identifiants
pubmed: 32522711
pii: S0969-9961(20)30235-7
doi: 10.1016/j.nbd.2020.104960
pmc: PMC7363568
mid: NIHMS1603253
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104960Subventions
Organisme : Medical Research Council
ID : MR/L023784/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG031581
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG053474
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/009076/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : UF1 AG032438
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG032438
Pays : United States
Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest A.M.G. has consulted for Cognition Therapeutics, Biogen, GSK, Illumina, Eisai, AbbVie and Pfizer and served on the SAB for Denali Therapeutics.
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