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. 2020 May;40(4):531-546.
doi: 10.1007/s10571-019-00751-y. Epub 2019 Nov 6.

Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases

Cristina Barbagallo  1 , Giovanni Mostile  2 , Gloriangela Baglieri  1 , Flavia Giunta  1 , Antonina Luca  2 , Loredana Raciti  2 , Mario Zappia  2 , Michele Purrello  1 , Marco Ragusa  3   4 , Alessandra Nicoletti  2
Affiliations

Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases

Cristina Barbagallo et al. Cell Mol Neurobiol. 2020 May.

Abstract

Neurodegenerative diseases (NDs) are age-dependent; among them, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent. Similarly, cerebrovascular damage can induce the development of vascular-related disorders that share common features with AD and PD, respectively, named vascular dementia (VD) and vascular parkinsonism (VP). To date, ND diagnosis is mainly clinical; therefore, since these disorders show similar symptoms, their correct discrimination may be difficult. We detected 23 ND-associated microRNAs (miRNAs) by literature mining and investigated their serum expression in a cohort of 139 patients including AD, PD, VD, and VP patients and healthy controls. TaqMan RT-PCR data showed that miR-23a upregulation was associated with an ongoing neurodegenerative process, similar to miR-22* and miR-29a, while let-7d, miR-15b, miR-24, miR-142-3p, miR-181c, and miR-222 showed an altered expression in Parkinson-like phenotypes, as well as miR-34b, miR-125b, and miR-130b in Alzheimer-like disorders. By computing logistic regression models and ROC curves, we identified signatures of neuro-miRNAs specific for each disease, showing good diagnostic performance. Interestingly, we found that miR-23a, miR-29a, miR-34b, and miR-125b exhibited a different distribution between exosomes and vesicle-free serum, suggesting a heterogeneity of secretion for these miRNAs. Our results suggest that miRNA signatures could discriminate in a non-invasive manner neurodegenerative disorders, thus improving clinical diagnoses.

Keywords: Alzheimer’s disease; Exosomes; Parkinson’s disease; Vascular dementia; Vascular parkinsonism; microRNAs.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Expression of miRNAs in AD, VD, PD, and VP patients and unaffected participants. Expression is presented as fold change, with a color-coded scale representing downregulation in green and upregulation in red. Statistical significance is shown by yellow asterisks: *p ≤ 0.05, **p ≤ 0.005, ***p ≤ 0.0005
Fig. 2
Fig. 2
Validation of differentially expressed miRNAs. Boxplots showing differential expression of miRNAs in the enlarged cohort in all the analyzed comparisons: a AD versus CTRL, b VD versus CTRL, c AD versus VD, d PD versus CTRL, e VP versus CTRL, f PD versus VP, and g ND versus CTRL. *p ≤ 0.05, **p ≤ 0.005, ***p ≤ 0.0005
Fig. 3
Fig. 3
Correlation between DE miRNAs and clinical parameters. Heatmap showing correlation between: a AD and VD patients, considered separately and as a unique macro-group, b PD and VP patients, considered separately and as a unique macro-group, and c ND patients, including both AD and PD patients. A color-coded scale depicts the Pearson or Spearman coefficient, showing negative correlation in green and positive correlation in red. *p ≤ 0.05, **p ≤ 0.005
See this image and copyright information in PMC

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