Cited by 55Amyotrophic Lateral Sclerosis ResearchExtracellular vesicles in diseaseMicroRNA in disease regulation

miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis

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Banack, Sandra Anne, Dunlop, Rachael Anne, Stommel, Elijah W., Mehta, Paul, Cox, Paul Alan·2022·Journal of the Neurological Sciences

Abstract

BACKGROUND AND OBJECTIVES: We examined miRNA biomarkers for ALS extracted from extracellular vesicles in blood samples using a large and diverse patient and control population. Different blood collection and storage protocols by different investigators could impact repeatability of miRNA analysis. We tested the hypotheses that miRNA extracted from extracellular vesicles using immunoaffinity purification techniques are robust and repeatable across investigators, laboratories and in a broad ALS population. METHODS: De-identified patient blood plasma samples obtained from the U.S. National ALS Biorepository were compared with plasma from non-ALS controls. Extracellular vesicles were extracted and isolated using L1CAM immunoaffinity purification. Total RNA was extracted, and miRNA quantified using qPCR following careful quality control measures. Gene fold expressions of eight miRNAs were compared using a Mann-Whitney two-tailed test. RESULTS: One hundred blinded, blood plasma samples were analyzed. Thirty-five men and 15 women with ALS were compared with controls consisting of 30 men and 20 women. None of the ALS patient cohort reported family members with ALS suggesting sporadic ALS. Five of the eight biomarkers previously published were found to significantly discriminate ALS patient samples from control samples. DISCUSSION: The methods used in this study provide a repeatable measure of miRNA biomarkers that statistically differentiate ALS patient samples from control samples. The broad inclusion criteria for both the ALS patient cohort and controls along with the collection of blood samples by different investigators suggest that these methods are robust and represent good candidates for further research and development aimed at clinical application.

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Crossref · 10.1016/j.jns.2022.120396

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  • miR-146a-5p is up-regulated while miR-4454 is down-regulated in blood plasma-derived EVs of ALS patients compared to healthy controls.

    “Banack et al. confirmed previous studies reporting that miR-146a-5p is up-regulated while miR-4454 is down-regulated in the blood plasma-derived EVs of ALS patients compared to healthy controls [267].”

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Authors
Banack, S. A., Dunlop, R. A., Stommel, E. W., Mehta, P., & Cox, P. A.
Affiliations
  • Dartmouth–Hitchcock Medical Center (US)
  • Centers for Disease Control and Prevention (US)
Corresponding author
Cox, Paul Alan
Venue
Journal of the Neurological Sciences
Publisher
Elsevier BV
Published
2022-11
Volume
442
Pages
120396
ISSN
0022-510X (ISSN-L)
OpenAlex
W4293522954
Cited by
54
References
52
Citations by year
2026: 7 · 2025: 13 · 2024: 18 · 2023: 12 · 2022: 4
FWCI
6.34
Type
journal article
Language
en
Open access
Locations
  • Journal of the Neurological Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Centers for Disease Control and Prevention
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
amyotrophic lateral sclerosis, microRNA biomarkers, extracellular vesicles, blood plasma, biomarker reproducibility, sporadic ALS, plasma microRNA expression
MeSH terms
Extracellular Vesicles, Amyotrophic Lateral Sclerosis, Female, Humans, Male, Biomarkers, MicroRNAs, Neural Cell Adhesion Molecule L1

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