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

  • Cristina Barbagallo
  • Giovanni Mostile
  • Gloriangela Baglieri
  • Flavia Giunta
  • Antonina Luca
  • Loredana Raciti
  • Mario Zappia
  • Michele Purrello
  • Marco RagusaEmail author
  • Alessandra Nicoletti
Original Research

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

microRNAs Alzheimer’s disease Parkinson’s disease Vascular dementia Vascular parkinsonism Exosomes 

Abbreviations

AD

Alzheimer’s disease

AUC

Area under the curve

CI

Confidence interval

CNS

Central nervous system

CSF

Cerebrospinal fluid

CTRL

Unaffected controls

DE

Differentially expressed

HY

Hoeh–Yahr

miRNA

microRNA

MMSE

Mini-mental state examination

NINCDS/ADRDA

National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association

ND

Neurodegenerative disease

OR

Odds ratio

PD

Parkinson’s disease

ROC

Receiver operating characteristic

UPDRS-ME

Unified Parkinson’s Disease Rating Scale Motor Examination

VD

Vascular dementia

VP

Vascular parkinsonism

Notes

Acknowledgements

The authors wish to thank the Scientific Bureau of the University of Catania for language support.

Authors Contributions

MR, AN, MP, and MZ designed and conceived the experiments. AN, GM, AL, and LR obtained and characterized biological samples from patients. CB, GB, and FG performed the experiments. CB, GM, and MR contributed to the analysis and interpretation of data. CB, MR, GM, and AN wrote the paper. All authors read and approved the final manuscript.

Funding

This study was supported by the University of Catania through Finanziamento della Ricerca 2014 and 2016/2018 Department Research Plan of University of Catania (second line of intervention).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethical committee of the Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele, Catania, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10571_2019_751_MOESM1_ESM.xlsx (21 kb)
Supplementary material 1 (XLSX 21 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • 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
    • 1
    • 3
    Email author
  • Alessandra Nicoletti
    • 2
  1. 1.Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. SichelUniversity of CataniaCataniaItaly
  2. 2.Department “G.F. Ingrassia”, Section of NeurosciencesUniversity of CataniaCataniaItaly
  3. 3.Oasi Research Institute - IRCCSTroinaItaly

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