Oncotarget

Research Papers: Pathology:

Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease

YaXing Gui _, Hai Liu, LiShan Zhang, Wen Lv and XingYue Hu

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Oncotarget. 2015; 6:37043-37053. https://doi.org/10.18632/oncotarget.6158

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Abstract

YaXing Gui1, Hai Liu1, LiShan Zhang1, Wen Lv1 and XingYue Hu1

1 Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Correspondence to:

YaXing Gui, email:

Keywords: Parkinson’s diseases (PD), Alzheimer’s diseases (AD), cerebrospinal fluid (CSF), exosome, microRNA, Pathology Section

Received: May 24, 2015 Accepted: September 30, 2015 Published: October 19, 2015

Abstract

The differential diagnosis of Parkinson’s diseases (PD) is challenging, especially in the early stages of the disease. We developed a microRNA profiling strategy for exosomal miRNAs isolated from cerebrospinal fluid (CSF) in PD and AD. Sixteen exosomal miRNAs were up regulated and 11 miRNAs were under regulated significantly in PD CSF when compared with those in healthy controls (relative fold > 2, p < 0.05). MiR-1 and miR-19b-3p were validated and significantly reduced in independent samples. While miR-153, miR-409-3p, miR-10a-5p, and let-7g-3p were significantly over expressed in PD CSF exosome. Bioinformatic analysis by DIANA-mirPath demonstrated that Neurotrophin signaling, mTOR signaling, Ubiquitin mediated proteolysis, Dopaminergic synapse, and Glutamatergic synapse were the most prominent pathways enriched in quantiles with PD miRNA patterns. Messenger RNA (mRNA) transcripts [amyloid precursor protein, APP), α-synuclein (α-syn), Tau, neurofilament,light gene (NF-L), DJ-1/PARK7, Fractalkine and Neurosin] and long non-coding RNAs (RP11-462G22.1 and PCA3) were differentially expressed in CSF exosomes in PD and AD patients. These data demonstrated that CSF exosomal RNA molecules are reliable biomarkers with fair robustness in regard to specificity and sensitivity in differentiating PD from healthy and diseased (AD) controls.


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