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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, Kemal, Olcum, Melis, Uzuner, Hamdiye, Karakülah, Gökhan, Yener, Gorsev, Genc, Sermin·2022·Journal of Molecular Neuroscience

Abstract

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 po…

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Metadata

Authors
Durur, D. Y., Tastan, B., Ugur Tufekci, K., Olcum, M., Uzuner, H., Karakülah, G., Yener, G., & Genc, S.
Venue
Journal of Molecular Neuroscience
Published
2022-04-29
Volume
72
Issue
6
Pages
1182-1194
ISSN
  • 0895-8696
  • 1559-1166
Cited by
46
References
6
Language
en

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CoChat. (2026). Citation check: Alteration of miRNAs in Small Neuron-Derived Extracellular Vesicles of Alzheimer's Disease Patients and the Effect of Extracellular Vesicles on Microglial Immune Responses. https://app.cochat.ai/papers/10.1007/s12031-022-02012-y
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Durur, D. Y., Tastan, B., Ugur Tufekci, K., Olcum, M., Uzuner, H., Karakülah, G., Yener, G., & Genc, S. (2022). Alteration of miRNAs in Small Neuron-Derived Extracellular Vesicles of Alzheimer's Disease Patients and the Effect of Extracellular Vesicles on Microglial Immune Responses. Journal of Molecular Neuroscience. https://doi.org/10.1007/s12031-022-02012-y