Altered Extracellular Vesicle MiRNA Profile in Prodromal Alzheimer's Disease

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Oct 14

PMID 37834197

Authors

Caterina Visconte

Chiara Fenoglio

Maria Serpente

Paola Muti

Andrea Sacconi

Marta Rigoni

Andrea Arighi

Vittoria Borracci

Marina Arcaro

Beatrice Arosio

Evelyn Ferri

Maria Teresa Golia

Elio Scarpini

Daniela Galimberti

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are nanosized vesicles released by almost all body tissues, representing important mediators of cellular communication, and are thus promising candidate biomarkers for neurodegenerative diseases like Alzheimer's disease (AD). The aim of the present study was to isolate total EVs from plasma and characterize their microRNA (miRNA) contents in AD patients. We isolated total EVs from the plasma of all recruited subjects using ExoQuickULTRA exosome precipitation solution (SBI). Subsequently, circulating total EVs were characterized using Nanosight nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. A panel of 754 miRNAs was determined with RT-qPCR using TaqMan OpenArray technology in a QuantStudio 12K System (Thermo Fisher Scientific). The results demonstrated that plasma EVs showed widespread deregulation of specific miRNAs (miR-106a-5p, miR-16-5p, miR-17-5p, miR-195-5p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-296-5p, miR-30b-5p, miR-532-3p, miR-92a-3p, and miR-451a), some of which were already known to be associated with neurological pathologies. A further validation analysis also confirmed a significant upregulation of miR-16-5p, miR-25-3p, miR-92a-3p, and miR-451a in prodromal AD patients, suggesting these dysregulated miRNAs are involved in the early progression of AD.

Citing Articles

Blood-based microRNAs as the potential biomarkers for Alzheimer's disease: evidence from a systematic review.

Fattahi F, Asadi M, Abed S, Kouchakali G, Kazemi M, Mansoori Derakhshan S Metab Brain Dis. 2024; 40(1):44.

PMID: 39607566 DOI: 10.1007/s11011-024-01431-7.

Efficient enzyme-free isolation of brain-derived extracellular vesicles.

Matamoros-Angles A, Karadjuzovic E, Mohammadi B, Song F, Brenna S, Meister S J Extracell Vesicles. 2024; 13(11):e70011.

PMID: 39508423 PMC: 11541858. DOI: 10.1002/jev2.70011.

Plasma-derived Exosomal miR-25-3p and miR-23b-3p as Predictors of Response to Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

Jing Z, Guo Z, Zhang C Technol Cancer Res Treat. 2024; 23:15330338241289520.

PMID: 39380461 PMC: 11465297. DOI: 10.1177/15330338241289520.

miR-92a-3p and miR-320a are Upregulated in Plasma Neuron-Derived Extracellular Vesicles of Patients with Frontotemporal Dementia.

Manzini V, Cappelletti P, Orefice N, Brentari I, Rigby M, Lo Giudice M Mol Neurobiol. 2024; 62(2):2573-2586.

PMID: 39138758 PMC: 11772464. DOI: 10.1007/s12035-024-04386-z.

Basic, Translational, and Clinical Research on Dementia.

Bagetta G, Bano D, Scuteri D Int J Mol Sci. 2024; 25(13).

PMID: 38999974 PMC: 11241002. DOI: 10.3390/ijms25136861.

References

Ventura A, Young A, Winslow M, Lintault L, Meissner A, Erkeland S . Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008; 132(5):875-86. PMC: 2323338. DOI: 10.1016/j.cell.2008.02.019. View

Dubois B, Feldman H, Jacova C, Hampel H, Molinuevo J, Blennow K . Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014; 13(6):614-29. DOI: 10.1016/S1474-4422(14)70090-0. View

von Schimmelmann M, Feinberg P, Sullivan J, Ku S, Badimon A, Duff M . Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration. Nat Neurosci. 2016; 19(10):1321-30. PMC: 5088783. DOI: 10.1038/nn.4360. View

Riancho J, Vazquez-Higuera J, Pozueta A, Lage C, Kazimierczak M, Bravo M . MicroRNA Profile in Patients with Alzheimer's Disease: Analysis of miR-9-5p and miR-598 in Raw and Exosome Enriched Cerebrospinal Fluid Samples. J Alzheimers Dis. 2017; 57(2):483-491. DOI: 10.3233/JAD-161179. View

Lukiw W . Variability in micro RNA (miRNA) abundance, speciation and complexity amongst different human populations and potential relevance to Alzheimer's disease (AD). Front Cell Neurosci. 2013; 7:133. PMC: 3753559. DOI: 10.3389/fncel.2013.00133. View

Liang X, Fa W, Wang N, Peng Y, Liu C, Zhu M . Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4. Aging Cell. 2022; 22(1):e13748. PMC: 9835579. DOI: 10.1111/acel.13748. View

Kim Y, Kim S, Park Y, Park J, Lee J, Kim B . miR-16-5p is upregulated by amyloid β deposition in Alzheimer's disease models and induces neuronal cell apoptosis through direct targeting and suppression of BCL-2. Exp Gerontol. 2020; 136:110954. DOI: 10.1016/j.exger.2020.110954. View

Mogilyansky E, Rigoutsos I . The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 2013; 20(12):1603-14. PMC: 3824591. DOI: 10.1038/cdd.2013.125. View

Pathan M, Fonseka P, Chitti S, Kang T, Sanwlani R, Van Deun J . Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles. Nucleic Acids Res. 2018; 47(D1):D516-D519. PMC: 6323905. DOI: 10.1093/nar/gky1029. View

10.

Zhu H, Wang L, Wang M, Song B, Tan S, Teng J . MicroRNA-195 downregulates Alzheimer's disease amyloid-β production by targeting BACE1. Brain Res Bull. 2012; 88(6):596-601. DOI: 10.1016/j.brainresbull.2012.05.018. View

11.

Lugli G, Cohen A, Bennett D, Shah R, Fields C, Hernandez A . Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered Expression and Prospects for Biomarkers. PLoS One. 2015; 10(10):e0139233. PMC: 4591334. DOI: 10.1371/journal.pone.0139233. View

12.

Blennow K . A Review of Fluid Biomarkers for Alzheimer's Disease: Moving from CSF to Blood. Neurol Ther. 2017; 6(Suppl 1):15-24. PMC: 5520819. DOI: 10.1007/s40120-017-0073-9. View

13.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

14.

Liss J, Seleri Assuncao S, Cummings J, Atri A, Geldmacher D, Candela S . Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer's disease (MCI and dementia) in primary care: a review and synthesis. J Intern Med. 2021; 290(2):310-334. PMC: 8359937. DOI: 10.1111/joim.13244. View

15.

Xiao T, Zhang W, Jiao B, Pan C, Liu X, Shen L . The role of exosomes in the pathogenesis of Alzheimer' disease. Transl Neurodegener. 2017; 6:3. PMC: 5289036. DOI: 10.1186/s40035-017-0072-x. View

16.

Zhang B, Chen C, Wang A, Lin Q . MiR-16 regulates cell death in Alzheimer's disease by targeting amyloid precursor protein. Eur Rev Med Pharmacol Sci. 2015; 19(21):4020-7. View

17.

Mertens J, Herdy J, Traxler L, Schafer S, Schlachetzki J, Bohnke L . Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer's patients. Cell Stem Cell. 2021; 28(9):1533-1548.e6. PMC: 8423435. DOI: 10.1016/j.stem.2021.04.004. View

18.

Petrocca F, Vecchione A, Croce C . Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008; 68(20):8191-4. DOI: 10.1158/0008-5472.CAN-08-1768. View

19.

Laugesen A, Hojfeldt J, Helin K . Role of the Polycomb Repressive Complex 2 (PRC2) in Transcriptional Regulation and Cancer. Cold Spring Harb Perspect Med. 2016; 6(9). PMC: 5008062. DOI: 10.1101/cshperspect.a026575. View

20.

Hebert S, Horre K, Nicolai L, Bergmans B, Papadopoulou A, Delacourte A . MicroRNA regulation of Alzheimer's Amyloid precursor protein expression. Neurobiol Dis. 2008; 33(3):422-8. DOI: 10.1016/j.nbd.2008.11.009. View