Differential Expression of Plasma Exo-miRNA in Neurodegenerative Diseases by Next-Generation Sequencing.

Chao Nie,Hefu Zhen,Jingyu Ye,Xiuqing Zhang,Zhili Liu,Yan Yang,Mei Guo,Yuzhe Sun

doi:10.3389/fnins.2020.00438

Abstract

Neurodegenerative diseases encompass a wide variety of pathological conditions caused by a loss of neurons in the central nervous system (CNS) and are severely debilitating. Exosome contains bio-signatures of great diagnostic and therapeutic value. There is proof that exosomal proteins can be biomarkers for Alzheimer’s disease (AD) and Parkinson’s disease (PD). MicroRNAs in exosome has potential to be an important source of biomarkers for neurodegenerative diseases. Here, we report exosomal microRNA performance of human plasma in neurodegenerative diseases by small RNA sequencing. A wide range of altered exo-miRNA expression levels were detected in both AD and PD patients. Down-regulated miRNAs in AD samples were enriched in ECM-receptor interaction pathway and both up-/down-regulated miRNAs in PD samples were enriched in fatty acid biosynthesis pathway. Compared to the control, 8 miRNAs were found to be significantly elevated/declined in AD and PD samples, of which 4 miRNAs were newly identified. Additionally, two exosome isolating methods were compared and the reproducibility of plasma exo-miRNA expression was confirmed, suggesting the feasibility of large-scale clinical application of this method. This study revealed exo-miRNA expression levels in neurodegenerative diseases, proposed new biomarkers and their potential functional pathway for AD and PD, confirmed the reproductivity of exo-miRNA profiles by using a different exosome isolating method, and compared the results with plasma miRNA expression. Therefore, this study also provides a precedent for identifying exosomal biomarkers of neurodegenerative diseases in plasma by high-throughput sequencing and it could extend the therapeutic repertoire of exosomal biomarkers.

Highlights

Neurodegenerative diseases are a group of disorders that are characterized by the progressive degeneration of the function and structure of the central nervous system (CNS) (Gao and Hong, 2008)
The corresponding miRNA expression levels of Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) originate from a loss of neurons in the CNS (Tan et al, 2015)
The sample size of AD and PD limits the accuracy of the biomarker selection

Summary

Introduction

Neurodegenerative diseases are a group of disorders that are characterized by the progressive degeneration of the function and structure of the central nervous system (CNS) (Gao and Hong, 2008). Traditional diagnosis of neurodegenerative diseases usually uses biomarkers in cerebrospinal fluid (CSF) or positron. Using peripheral blood to detect neurodegenerative biomarkers satisfies the rapid and safe requirement of chronic disease prediction (Valadi et al, 2007; Schwarzenbach et al, 2014). Pathological neurons release huge amount of exosome, some of which spread to peripheral blood, and cause the change of exosome-derived contents (Wood et al, 2011). A newly study showed that there is concordance between the assessment of Aβ42, T-tau, and P-T181-tau in CSF and plasma exosomes suggesting that lots of exosomes extracted from human plasma are derived from brain (Jia et al, 2019). Exosomal proteins as biomarkers in different human body fluids have been widely studied.

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