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

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.

• Authors: Sandra Anne Banack, Rachael Anne Dunlop, Elijah W Stommel, Paul Mehta, Paul Alan Cox
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 442 Pg. 120396 (11 15 2022) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 36081303 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• MicroRNAs
• Neural Cell Adhesion Molecule L1
• Biomarkers

Topics

• Male
• Humans
• Female
• Amyotrophic Lateral Sclerosis (diagnosis, genetics)
• MicroRNAs (metabolism)
• Neural Cell Adhesion Molecule L1 (metabolism)
• Extracellular Vesicles (metabolism)
• Biomarkers