Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases
Abstract
:1. Introduction
2. Results
2.1. miRNAs Selectively Traffic into SEVs and LEVs
2.2. miRNAs Expression Profiles and Common Pathways in SEVs and LEVs of NDs
2.3. Specific miRNAs Pathway Analysis in SEVs of NDs
2.4. Specific miRNAs Pathway Analysis in LEVs of NDs
3. Discussion
4. Materials and Methods
4.1. Study Subjects
4.2. LEVs and SEVs Isolation
4.3. RNA Extraction
4.4. RNA Libraries Preparations
4.5. Bioinformatic Data Analysis
4.6. Pathways Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
ALS | Amyotrophic Lateral Sclerosis |
CTRs | healthy controls |
DE miRNAs | differentially expressed miRNAs |
ESCRT | Endosomal Sorting Complexes Required for Transport |
EVs | extracellular vesicles |
EXOs | exosomes |
FTD | frontotemporal dementia |
GWAS | Genome-wide association studies |
ILVs | intraluminal vesicles |
IPA | Ingenuity pathway analysis |
LBs | Lewy bodies |
LEVs | large extracellular vesicles |
lncRNA | long non coding RNA |
miRNA | microRNA |
MVs | microvesicles |
NDs | neurodegenerative diseases |
PCA | principal component analysis |
PD | Parkinson’s disease |
RBPs | RNA-binding proteins |
SEVs | small extracellular vesicles |
SN | substantia nigra |
SNPs | single nucleotide polymorphisms |
TLRs | Toll like receptors |
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miRNAs | AD | FTD | ALS | PD | ||||
---|---|---|---|---|---|---|---|---|
SEVs | LEVs | SEVs | LEVs | SEVs | LEVs | SEVs | LEVs | |
up-regulated | 17 | 10 | 49 | 113 | 80 | 128 | 85 | 87 |
down-regulated | 16 | 3 | 39 | 17 | 29 | 69 | 19 | 22 |
Total | 33 | 13 | 88 | 130 | 109 | 197 | 104 | 109 |
miRNA | ||
---|---|---|
NDs | Common miRNAs in SEVs and LEVs (%) | |
SEVs | LEVs | |
AD | 18.2 | 46.2 |
FTD | 38.6 | 25.2 |
ALS | 61.5 | 34 |
PD | 32.7 | 31.2 |
Patients | Sex | Age | Education (years) | Disease Duration (months) | Familiarity | cMMSE † | Tau †† | pTau ††† | Aβ †††† 1-42 |
---|---|---|---|---|---|---|---|---|---|
FTD1 | M | 54 | 8 | 24 | No | 8,97 | <10 | 10 | 683 |
FTD2 | F | 57 | 8 | 36 | No | 15.74 | 419 | 43 | 616 |
FTD3 | M | 70 | 8 | 36 | No | 18 | NA | NA | NA |
FTD4 | M | 62 | 8 | 34 | No | 17 | 164 | 42 | 1312 |
FTD5 | M | 52 | 8 | 34 | No | 17.97 | 195 | 42 | 1378 |
FTD6 | M | 69 | 11 | 36 | No | 21 | NA | NA | NA |
FTD7 | M | 56 | 13 | 60 | No | 17.99 | <10 | 7 | 360 |
FTD8 | M | 49 | 5 | 12 | No | 18.31 | 799 | 68 | 1780 |
FTD9 | F | 75 | 8 | 44 | No | 17 | NA | NA | NA |
Column Title | CTRs | AD | FTD | ALS | PD |
---|---|---|---|---|---|
Recruited subjects | 6 | 6 | 9 | 6 | 9 |
Age (mean ± SD) | 55 ± 5.2 | 77 ± 3.7 | 60 ± 6.7 | 72 ± 6.3 | 69 ± 3.6 |
Males % | 43% | 50% | 78% | 50% | 60% |
Females % | 67% | 50% | 22% | 50% | 40% |
Patients | Sex | Age | Education (years) | Disease Duration (months) | Familiarity | Onset | Imaging † | MMSE †† | CDR ††† |
---|---|---|---|---|---|---|---|---|---|
AD1 | M | 78 | 5 | 50 | No | Amnesic | 1.3 | 15 | 2 |
AD2 | M | 70 | 8 | 48 | Yes | Amnesic | 1 | 19 | 1.5 |
AD3 | F | 79 | 5 | 48 | No | Amnesic | 2 | 20 | 1 |
AD4 | M | 77 | 5 | 40 | No | Amnesic | 1 | 13 | 2 |
AD5 | F | 82 | 5 | 38 | Yes | Amnesic | 1 | 18 | 1 |
AD6 | F | 76 | 5 | 42 | Yes | Amnesic | 2.3 | 17 | 2 |
Patients | Sex | Age | Education (years) | Disease Duration (months) | Familiarity | Site of Onset | ALSFRS † | Therapy (Riluzole) |
---|---|---|---|---|---|---|---|---|
ALS1 | F | 69 | 13 | 19 | No | Spinal | 9 | |
ALS2 | F | 70 | NA | 52 | No | Spinal | 29 | 19 |
ALS3 | F | 69 | NA | 11 | No | Spinal | 34 | 20 |
ALS4 | M | 71 | 5 | 24 | No | Spinal | 46 | 13 |
ALS5 | M | 72 | 13 | 67 | No | Spinal | 28 | 18 |
ALS6 | M | 67 | 5 | 28 | No | Spinal | 40 | 17 |
Patients | Sex | Age | Education (years) | Disease Duration (years) | Familiarity | Affected Side | UPDRS III † | Therapy LEDD †† | Disorders of Behaviour |
---|---|---|---|---|---|---|---|---|---|
PD1 | F | 70 | NA | 8 | No | Right | 12 | 350 | No |
PD2 | M | 73 | NA | 7 | Yes | Right | 10 | 320 | ICD |
PD3 | M | 68 | 8 | 19 | No | Left | 44 | 800 | ICD |
PD4 | M | 69 | NA | 13 | Yes | Right | 18 | 500 | No |
PD5 | F | 73 | 8 | 10 | Yes | Right | 17 | 1000 | No |
PD6 | M | 76 | NA | 7 | No | Right | 18 | 650 | No |
PD7 | F | 68 | NA | 6 | No | Right | 20 | 600 | No |
PD8 | M | 76 | 8 | 13 | Yes | Left | 35 | 690 | No |
PD9 | F | 73 | NA | 13 | Yes | Left | 15 | 350 | ICD |
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Sproviero, D.; Gagliardi, S.; Zucca, S.; Arigoni, M.; Giannini, M.; Garofalo, M.; Olivero, M.; Dell’Orco, M.; Pansarasa, O.; Bernuzzi, S.; et al. Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases. Int. J. Mol. Sci. 2021, 22, 2737. https://doi.org/10.3390/ijms22052737
Sproviero D, Gagliardi S, Zucca S, Arigoni M, Giannini M, Garofalo M, Olivero M, Dell’Orco M, Pansarasa O, Bernuzzi S, et al. Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases. International Journal of Molecular Sciences. 2021; 22(5):2737. https://doi.org/10.3390/ijms22052737
Chicago/Turabian StyleSproviero, Daisy, Stella Gagliardi, Susanna Zucca, Maddalena Arigoni, Marta Giannini, Maria Garofalo, Martina Olivero, Michela Dell’Orco, Orietta Pansarasa, Stefano Bernuzzi, and et al. 2021. "Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases" International Journal of Molecular Sciences 22, no. 5: 2737. https://doi.org/10.3390/ijms22052737