UMMS Affiliation
Department of Neurology
Publication Date
2020-06-09
Document Type
Article
Disciplines
Amino Acids, Peptides, and Proteins | Biological Factors | Nervous System Diseases | Neurology | Neuroscience and Neurobiology
Abstract
OBJECTIVE: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects.
METHODS: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from > /=2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and slow-progression subgroups using the ALS Functional Rating Scale-Revised change rate. We compared cytokines/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with C9orf72 mutations.
RESULTS: We found significant elevations of cytokines, including MCP-1, IL-18, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast-progression and C9orf72 mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups.
INTERPRETATION: Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast-progression patients and may be used to select similar patient subsets in clinical trials.
Keywords
amyotrophic lateral sclerosis, ALS, biomarkers, cytokines, neurofilaments
Rights and Permissions
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
DOI of Published Version
10.1002/acn3.51078
Source
Huang F, Zhu Y, Hsiao-Nakamoto J, Tang X, Dugas JC, Moscovitch-Lopatin M, Glass JD, Brown RH Jr, Ladha SS, Lacomis D, Harris JM, Scearce-Levie K, Ho C, Bowser R, Berry JD. Longitudinal biomarkers in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2020 Jun 9. doi: 10.1002/acn3.51078. Epub ahead of print. PMID: 32515902. Link to article on publisher's site
Journal/Book/Conference Title
Annals of clinical and translational neurology
Related Resources
PubMed ID
32515902
Repository Citation
Huang F, Zhu Y, Hsiao-Nakamoto J, Tang X, Dugas JC, Moscovitch-Lopatin M, Glass JD, Brown RH, Ladha SS, Lacomis D, Harris JM, Scearce-Levie K, Ho C, Bowser R, Berry JD. (2020). Longitudinal biomarkers in amyotrophic lateral sclerosis. Open Access Publications by UMMS Authors. https://doi.org/10.1002/acn3.51078. Retrieved from https://escholarship.umassmed.edu/oapubs/4267
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Biological Factors Commons, Nervous System Diseases Commons, Neurology Commons, Neuroscience and Neurobiology Commons