Alteration of miRNAs in Small Neuron-Derived Extracellular Vesicles of Alzheimer's Disease Patients and the Effect of Extracellular Vesicles on Microglial Immune Responses.
Durur, Devrim Yagmur; TASTAN, Bora; Ugur Tufekci, Kemalet al.
2022 • In Journal of Molecular Neuroscience, 72 (6), p. 1182 - 1194
[en] Alzheimer's disease (AD) is one of the most severe neurodegenerative diseases observed in the elderly population. Although the hallmarks of AD have been identified, the methods for its definitive diagnosis and treatment are still lacking. Extracellular vesicles (EVs) have become a promising source for biomarkers since the identification of their content. EVs are released from multiple cell types and, when released from neurons, they pass from the brain to the blood with their cargo molecules. Hence, neuron-specific EV-resident microRNAs (miRNAs) are promising biomarkers for diagnosis of AD. This study aimed to identify altered miRNA content in small neuron-derived extracellular vesicles (sNDEVs) isolated from AD patients and healthy individuals. Furthermore, we examined the role of sNDEV-resident miRNAs in neuron-glia cellular interaction to understand their role in AD propagation. We identified 10 differentially expressed miRNAs in the sNDEVs of patients via next-generation sequencing and validated the most dysregulated miRNA, let-7e, with qRT-PCR. Let-7e was significantly increased in the sNDEVs of AD patients compared with those of healthy controls in a larger cohort. First, we evaluated the diagnostic utility of let-7e via ROC curve analysis, which revealed an AUC value of 0.9214. We found that IL-6 gene expression was increased in human microglia after treatment with sNDEVs of AD patients with a high amount of let-7e. Our study suggests that sNDEV-resident let-7e is a potential biomarker for AD diagnosis, and that AD patient-derived sNDEVs induce a neuroinflammatory response in microglia.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Durur, Devrim Yagmur; Biomedicine and Genome Center, Izmir, Turkey ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University Health Campus, Izmir, Turkey
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Biomedicine and Genome Center, Izmir, Turkey ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University Health Campus, Izmir, Turkey
Ugur Tufekci, Kemal; Vocational School of Health Services, Izmir Democracy University, Izmir, Turkey
Olcum, Melis; Biomedicine and Genome Center, Izmir, Turkey
Uzuner, Hamdiye; Biomedicine and Genome Center, Izmir, Turkey ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University Health Campus, Izmir, Turkey
Karakülah, Gökhan; Biomedicine and Genome Center, Izmir, Turkey ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University Health Campus, Izmir, Turkey
Yener, Gorsev; Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir, Turkey ; Department of Neurology, Faculty of Medicine, Izmir University of Economics, Izmir, Turkey
Genc, Sermin ; Biomedicine and Genome Center, Izmir, Turkey. sermin.genc@deu.edu.tr ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University Health Campus, Izmir, Turkey. sermin.genc@deu.edu.tr ; Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir, Turkey. sermin.genc@deu.edu.tr
External co-authors :
yes
Language :
English
Title :
Alteration of miRNAs in Small Neuron-Derived Extracellular Vesicles of Alzheimer's Disease Patients and the Effect of Extracellular Vesicles on Microglial Immune Responses.
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