A microRNA diagnostic biomarker for amyotrophic lateral sclerosis

Sandra Anne Banack; Rachael A Dunlop; Paul Mehta; Hiroshi Mitsumoto; Stewart P Wood; Moon Han; Paul Alan Cox

doi:10.1093/braincomms/fcae268

journal article Open Access Jan 01, 2024

A microRNA diagnostic biomarker for amyotrophic lateral sclerosis

Sandra Anne Banack

Rachael A Dunlop

Paul Mehta Hiroshi Mitsumoto Stewart P Wood Moon Han Paul Alan Cox

Brain Communications Vol. 6 No. 5 · Oxford University Press (OUP)

View at Publisher Save 10.1093/braincomms/fcae268

Abstract

Abstract
Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific. Extracellular vesicles were extracted from blood plasma obtained from individuals diagnosed with amyotrophic lateral sclerosis, primary lateral sclerosis, Parkinson’s disease and healthy controls. Immunoaffinity purification was used to create a neural-enriched extracellular vesicle fraction. MicroRNAs were measured across sample cohorts using real-time polymerase chain reaction. A Kruskal–Wallis test was used to assess differences in plasma microRNAs followed by post hoc Mann–Whitney tests to compare disease groups. Diagnostic accuracy was determined using a machine learning algorithm and a logistic regression model. We identified an eight-microRNA diagnostic signature for blood samples from amyotrophic lateral sclerosis patients with high sensitivity and specificity and an area under the curve calculation of 98% with clear statistical separation from neurological controls. The eight identified microRNAs represent disease-related biological processes consistent with amyotrophic lateral sclerosis. The direction and magnitude of gene fold regulation are consistent across four separate patient cohorts with real-time polymerase chain reaction analyses conducted in two laboratories from diverse samples and sample collection procedures. We propose that this diagnostic signature could be an aid to neurologists to supplement current clinical metrics used to diagnose amyotrophic lateral sclerosis.

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References

Details

Published: Jan 01, 2024
Vol/Issue: 6(5)
License: View

Authors

S

Sandra Anne Banack

Brain Chemistry Labs , Jackson, WY 83001 ,

R

Rachael A Dunlop

Brain Chemistry Labs , Jackson, WY 83001 ,

P

Paul Mehta

Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention , Atlanta, GA 30033 ,

H

Hiroshi Mitsumoto

Eleanor and Lou Gehrig MND/ALS Research Center, Department of Neurology, Columbia University Medical Center , New York, NY 10032 ,

S

Stewart P Wood

Brain Chemistry Labs , Jackson, WY 83001 ,

M

Moon Han

Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention , Atlanta, GA 30033 ,

P

Paul Alan Cox

Brain Chemistry Labs , Jackson, WY 83001 ,

Cite This Article

Sandra Anne Banack, Rachael A Dunlop, Paul Mehta, et al. (2024). A microRNA diagnostic biomarker for amyotrophic lateral sclerosis. Brain Communications, 6(5). https://doi.org/10.1093/braincomms/fcae268

A microRNA diagnostic biomarker for amyotrophic lateral sclerosis

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