Identification of blood serum micro‐RNAs associated with idiopathic and LRRK2 Parkinson's disease

Abstract

Blood-cell-free circulating micro-RNAs (miRNAs) have been proposed as potential accessible biomarkers for neurodegenerative diseases such as Parkinson's disease (PD). Here we analyzed the serum levels of 377 miRNAs in a discovery set of 10 idiopathic Parkinson's disease (IPD) patients, 10 PD patients carriers of the LRRK2 G2019S mutation (LRRK2 PD), and 10 controls by using real-time quantitative PCR-based TaqMan MicroRNA arrays. We detected candidate differentially expressed miRNAs, which were further tested in a first validation set consisting of 20 IPD, 20 LRRK2 PD, and 20 control samples. We found four statistically significant miRNAs that were downregulated in either LRRK2 or IPD (miR-29a, miR-29c, miR-19a, and miR-19b). Subsequently, we validated these findings in a third set of samples consisting of 65 IPD and 65 controls and confirmed the association of downregulated levels of miR-29c, miR-29a, and miR-19b in IPD. Differentially expressed miRNAs are predicted to target genes belonging to pathways related to ECM-receptor interaction, focal adhesion, MAPK, Wnt, mTOR, adipocytokine, and neuron projection. Results from our exploratory study indicate that downregulated levels of specific circulating serum miRNAs are associated with PD and suggest their potential use as noninvasive biomarkers for PD. Future studies should further confirm the association of these miRNAs with PD.

MicroRNA association with synucleinopathy conversion in rapid eye movement behavior disorder

“…The downregulation of miR-19b, miR-29a, and miR-29c has been previously reported in PD subjects in whom the presence of the prodromal phase was not investigated. 13,[17][18][19] Additionally, we report for the first time the association of miRNA serum levels with DLB. The overlapping association of miR-19b, miR-29a, and miR-29c in PD and DLB is in agreement with the concept that both conditions represent the same neurodegenerative disease but with different phenotypes.…”

“…Total RNA and miRNA were extracted using the miRNA-easy mini kit (Qiagen, Valencia, CA). RNA concentration was determined on a NanoDrop ND-3300 Fluorospectrometer (Thermo Scientific, Waltham, MA Based on our previous study, 13 we investigated the expression of miR-19b, miR-29a, and miR-29c using miR-17 and miR-106 as endogenous controls, and miR-19a as negative control not associated with PD. Samples were processed and quantified in parallel.…”

“…13 To further explore their possible role in the prodromal stage of synucleinopathies, in the present study we have investigated the expression levels of these 3 miRNAs in serum samples from IRBD patients, before and after clinical conversion to PD and DLB.…”

Extracellular microRNAs as messengers in the central and peripheral nervous system

“…Intriguingly, while RNA molecules in the cell tend to be short-lived, circulating microRNAs show much higher stability and are protected from degradation by endogenous RNases [14]. Altered levels of specific microRNAs in body fluids have been linked to a wide range of diseases, including disorders of the nervous system [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Serum microRNA levels were altered in children with autism spectrum disorders and salivary levels have been correlated with neurodevelopmental scores [15,16].…”

“…disease [17][18][19][20], Parkinson's disease [16,21], Huntington's disease [22] and multiple sclerosis [23,24], as well as glioma [25][26][27] and stroke [28]. MicroRNA levels in the CSF were used to differentiate between glioblastoma and brain metastatic cancers [27].…”