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. 2017 Jul:55:123-131.
doi: 10.1016/j.neurobiolaging.2017.03.027. Epub 2017 Apr 1.

Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic lateral sclerosis (ALS)

Rachel Waller  1 , Emily F Goodall  1 , Marta Milo  2 , Jonathan Cooper-Knock  1 , Marc Da Costa  1 , Esther Hobson  1 , Mbombe Kazoka  1 , Helen Wollff  1 , Paul R Heath  1 , Pamela J Shaw  1 , Janine Kirby  3
Affiliations

Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic lateral sclerosis (ALS)

Rachel Waller et al. Neurobiol Aging. 2017 Jul.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative condition characterized by loss of motor neurones and progressive muscle wasting. There is no diagnostic test for ALS therefore robust biomarkers would not only be valuable for diagnosis, but also for the classification of disease subtypes, monitoring responses to drugs and tracking disease progression. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states with increasing exploration in neurodegenerative disorders. We hypothesize that circulating blood-based miRNAs will serve as biomarkers and use miRNA profiling to determine miRNA signatures from the serum of sporadic ALS patients compared to healthy controls and patients with diseases that mimic ALS. A number of differentially expressed miRNAs were identified in each set of patient comparisons. Validation in an additional patient cohort showed that miR-206 and miR-143-3p were increased and miR-374b-5p was decreased compared to controls. A continued change in miRNA expression persisted during disease progression indicating the potential use of these particular miRNAs as longitudinal biomarkers in ALS.

Keywords: Amyotrophic lateral sclerosis; Biomarker; MicroRNA; Polymerase chain reaction; Serum.

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Figures

Fig. 1
Fig. 1
Qlucore output: example PCA plots and heatmaps, t-tests p ≤ 0.05. (A) ALS (yellow) versus control (blue), (B) ALS versus myopathy (turquoise), (C) ALS versus noninflammatory neuropathy (green). Abbreviations: ALS, amyotrophic lateral sclerosis; PCA, principal component analysis. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 2
Fig. 2
Significant miRNA expression in sALS (n = 23) versus control (n = 22) subjects as confirmed by qPCR. Unpaired t-test, error bars represent SD. Abbreviations: miRNA, microRNA; sALS, sporadic amyotrophic lateral sclerosis; SD, standard deviation.
Fig. 3
Fig. 3
Riluzole versus riluzole naïve patients. miRNA expression (miR-206, miR-143-3p and miR-374b-5p) in riluzole naïve (n = 10) and riluzole treated patients (n = 13) confirmed by qPCR. Unpaired t-test, error bars represent SD. Abbreviations: miRNA, microRNA; SD, standard deviation.
Fig. 4
Fig. 4
miRNA expression changes over time as confirmed by qPCR in 21 sALS patients. Unpaired t-test, error bars represent SD. Abbreviations: miRNA, microRNA; sALS, sporadic amyotrophic lateral sclerosis; SD, standard deviation.
Fig. 5
Fig. 5
Comparing miR-143-3p expression changes over time in 3 patient groups as confirmed by qPCR in bulbar (n = 5), upper (n = 6), and lower limb (n = 9) onset sALS patients. Mann–Whitney U test, error bars represent SD. Abbreviations: sALS, sporadic amyotrophic lateral sclerosis; SD, standard deviation.
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