Abstract
ObjectivesThere is a lack of effective biomarkers for neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia. Extracellular vesicle (EV) RNA cargo can have an interesting potential as a non-invasive biomarker for NDs. However, the knowledge about the abundance of EV-mRNAs and their contribution to neurodegeneration is not clear.MethodsLarge and small EVs (LEVs and SEVs) were isolated from plasma of patients and healthy volunteers (control, CTR) by differential centrifugation and filtration, and RNA was extracted. Whole transcriptome was carried out using next generation sequencing (NGS).ResultsCoding RNA (i.e., mRNA) but not long non-coding RNAs (lncRNAs) in SEVs and LEVs of patients with ALS could be distinguished from healthy CTRs and from other NDs using the principal component analysis (PCA). Some mRNAs were found in commonly deregulated between SEVs of patients with ALS and frontotemporal dementia (FTD), and they were classified in mRNA processing and splicing pathways. In LEVs, instead, one mRNA and one antisense RNA (i.e., MAP3K7CL and AP003068.3) were found to be in common among ALS, FTD, and PD. No deregulated mRNAs were found in EVs of patients with AD.ConclusionDifferent RNA regulation occurs in LEVs and SEVs of NDs. mRNAs and lncRNAs are present in plasma-derived EVs of NDs, and there are common and specific transcripts that characterize LEVs and SEVs from the NDs considered in this study.
Highlights
Disease-specific mechanisms for neurodegenerative diseases (NDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are more commonly investigated for specific therapeutic and diagnostic targets (Habib, 2018)
The purity of large EVs (LEVs) and small EVs (SEVs) was confirmed by the Western blot (WB) analysis, nanotracking particle analysis (NTA), and transmission electron microscopy (TEM) as we described previously (Sproviero et al, 2021)
Large extracellular vesicles (LEVs) and SEVs were separated by differential centrifugation
Summary
Disease-specific mechanisms for neurodegenerative diseases (NDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are more commonly investigated for specific therapeutic and diagnostic targets (Habib, 2018). It is known that RNA metabolism is a common factor in the pathogenesis of NDs, and numerous new studies have been investigating the role of miRNAs in EVs of NDs (Liu et al, 2017; Jiang et al, 2019; Soares Martins et al, 2021). On this subject, we have recently demonstrated that plasma-derived SEVs and LEVs from AD, PD, ALS, and FTD carry different miRNAs and have a common signature among the four NDs (Sproviero et al, 2021).
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