Extracellular Vesicles Derived From Plasma of Patients With Neurodegenerative Disease Have Common Transcriptomic Profiling

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.

Extracellular Vesicles in Amyotrophic Lateral Sclerosis

“…Sproviero et al reported 542 upregulated genes and 88 downregulated genes in plasma EVs from ALS patients. Gene ontology analysis from these results showed enrichment of genes involved in the regulation of transmembrane transport, leukocyte chemotaxis and transcription regulation [ 128 ].…”

Extracellular vesicles in the study of Alzheimer's and Parkinson's diseases: Methodologies applied from cells to biofluids

“…Further, comparison of mRNA species found in small and large EVs from AD, PD but also ALS and FTD cases, showed that small EVs were more enriched in mRNA species and that different mRNAs patterns were found between the two vesicles types isolated from all disease cases. No differently expressed mRNA species were found in small EVs from AD however mRNA species were changed in PD, ALS and FTD (Sproviero et al, 2022). In sum, in the same disease, both miRNA and mRNA cargo can differ between small and large EVs and this should also be considered in the search for novel biomarkers.…”

Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications

“…Stress events affect not only the amount of secreted EVs, but also their molecular composition, resulting in altered vesicles that can prospectively provide biomarkers for several diseases [ 64 ]. Indeed, they might act as reservoirs of dangerous molecules (e.g., unfolded proteins, mutated DNA, or pathogens) that could modify cell physiology and thus need to be eliminated through normal clearance [ 65 ]. For instance, it has been proposed that when the normal activity of the endoplasmic reticulum fails, due to stress events, cells release stressed EVs that trap damaged/unfolded proteins inside their lumen in order to preserve the endoplasmic reticulum homeostasis and cell vitality [ 66 ].…”