Identification of circulating microRNAs for the differential diagnosis of Parkinson's disease and Multiple System Atrophy

Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder which may be misdiagnosed with atypical conditions such as Multiple System Atrophy (MSA), due to overlapping clinical features. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in post-transcriptional gene regulation. We hypothesized that identification of a distinct set of circulating miRNAs (cmiRNAs) could distinguish patients affected by PD from MSA and healthy individuals. Results. Using TaqMan Low Density Array technology, we analyzed 754 miRNAs and found 9 cmiRNAs differentially expressed in PD and MSA patients compared to healthy controls. We also validated a set of 4 differentially expressed cmiRNAs in PD and MSA patients vs. controls. More specifically, miR-339-5p was downregulated, whereas miR-223*, miR-324-3p, and mir-24 were upregulated in both diseases. We found cmiRNAs specifically deregulated in PD (downregulation of miR-30c and miR-148b) and in MSA (upregulation of miR-148b). Finally, comparing MSA and PD, we identified 3 upregulated cmiRNAs in MSA serum (miR-24, miR-34b, miR-148b). Conclusions. Our results suggest that cmiRNA signatures discriminate PD from MSA patients and healthy controls and may be considered specific, non-invasive biomarkers for differential diagnosis.

Serum microRNA expression profiling in patients with multiple system atrophy

“…In agreement with a previous study, miR-223 was also upregulated in the present study (14). It has been demonstrated that upregulation of miR-223 is associated with the pathophysiology of infection, inflammation and cancer (30).…”

“…The results of the present study also identified that miR-24 and miR-223 were upregulated in MSA serum, as described previously (14). These results indicate that the methods used by the present study to determine the profile of miRNA are valid.…”

“…The hierarchical clustering analysis identified marked differences between the miRNA profiles of the MSA and the control groups. There are few reports on miRNA profiling in patients with MSA (14,15). It has been demonstrated that miR-24, miR-223 and miR-324-3p are upregulated in the serum of patients with MSA or PD (14), and a greater upregulation of miRNA/miR, microRNA; MSA, multiple system atrophy; P, parkinsonian form of MSA; C, cerebellar form of MSA; hsa, human (Homo sapiens).…”

MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment

“…Bioinformatics analysis of these miRNAs showed several biologic pathways and cellular function regulated from them, including cell proliferation, cell communication, and cell signalling. Importantly, these two miRNAs have been already reported as circulating in human body fluids (44)(45)(46)(47)(48)(49)(50). Even if further data are needed to confirm these preliminary findings, this is the first report highlighting the potential role of miRNAs quantification from the easily collectable SBM as a new biomarker to be further explored for embryo selection.…”

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

“…Vallelunga et al recently reported a set of nine specific miRNAs out of approximately 750 examined that could distinguish PD from controls and subjects with multiple system atrophy. 92 A nonoverlapping set of four specific miRNAs was found in an independent study to be downregulated in PD, including the genetic LRRK2-associated form of PD, versus controls.…”