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Altered Expression of Long Non-coding RNAs in Peripheral Blood Mononuclear Cells of Patients with Alzheimer’s Disease

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Abstract

Long non-coding RNAs (lncRNAs) are involved in many neurological conditions, and neurodegenerative disorders including Alzheimer’s disease (AD) regulate gene expression at transcriptional, post-transcriptional, and epigenetic levels. However, the roles of lncRNAs in the pathogenesis of AD remain unclear. In this study, we aimed to determine the expression of lncRNAs and also mRNAs in AD which may alter expression and contribute to the pathogenesis of the disease. Peripheral blood samples were obtained from patients admitted to the Neurology Department of Pamukkale University Medical Faculty (23 patients with AD, 33 control groups). Total RNA obtained from peripheral blood mononuclear cells (PBMC) of subjects with probable AD (n = 4) and healthy control groups (n = 4) was examined to determine the altered expression of lncRNAs and mRNAs in AD were evaluated by microarray analysis. Five lncRNAs with the highest end-to-end fold change (fc ≥ 2.0, p < 0.05) were identified and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). In our study, the profiles of lncRNAs and mRNAs that may be associated with Alzheimer’s disease were determined. A total of 14 lncRNAs and 35 mRNAs were determined as upregulated, and 20 lncRNAs and 73 mRNAs determined as downregulated as a result of microarray analysis in patients with AD compared with control groups (fold change ≥ 2.0, p < 0.05). From lncRNAs, expression of lncRNA TTC39C-AS1, lnc-AL445989.1-2, LINC01420, lnc-CSTB-1, and LOC401557 was confirmed by qRT-PCR. When assessed by KEGG analysis of AD PBMC lncRNA and mRNA profiles, TNF signaling pathway, PI3K/AKT, Ras, and MAPK pathways; glutamatergic, dopaminergic, and cholinergic synapses; GABA, and neurotrophin signaling pathways are found to be significant. This is the first known study to investigate lncRNA profiles in AD PBMCs. We think that these results may open a door to the understanding of AD pathogenesis targeted by lncRNAs.

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Acknowledgments

The authors thank Dr. Ahmet Dogucem Marangoz and Dr. Zeynep Unluturk in the Department of Neurology, Pamukkale University for their diligent assistance with the data collection for this study.

Funding

This study is supported by Pamukkale University Scientific Research Committee with the project number 2016SBE010.

Author information

Authors and Affiliations

  1. Department of Medical Biology, Health Sciences Institution, Dokuz Eylul University, İnciraltı, İzmir, Turkey

    Serap Kurt

  2. Department of Medical Biology, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Ayse Gaye Tomatir

  3. Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Pervin Elvan Tokgun

  4. Department of Neurology, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Cagatay Oncel

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  1. Serap Kurt
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  2. Ayse Gaye Tomatir
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  4. Cagatay Oncel
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Correspondence to Serap Kurt.

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All protocols used in this study were approved by the Ethics Committee of Pamukkale University Hospital, Turkey. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional committee.

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The authors declare that they have no conflict of interest.

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Kurt, S., Tomatir, A.G., Tokgun, P.E. et al. Altered Expression of Long Non-coding RNAs in Peripheral Blood Mononuclear Cells of Patients with Alzheimer’s Disease. Mol Neurobiol 57, 5352–5361 (2020). https://doi.org/10.1007/s12035-020-02106-x

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  • DOI: https://doi.org/10.1007/s12035-020-02106-x

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