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.
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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
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The authors wish to thank the Scientific Bureau of the University of Catania for language support.
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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).
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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.
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Barbagallo, C., Mostile, G., Baglieri, G. et al. Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases. Cell Mol Neurobiol 40, 531–546 (2020). https://doi.org/10.1007/s10571-019-00751-y
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DOI: https://doi.org/10.1007/s10571-019-00751-y