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NLRP1 and NTN1, Deregulated Blood Differentially Methylated Regions in Mild Cognitive Impairment Patients

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Abstract

Epigenetic dysregulation has been known to be involved in neurodegenerative diseases, including amnestic mild cognitive impairment (MCI). The aim of this study was to investigate the genome-wide DNA methylation analysis, in order to identify epigenetic dysregulation in blood from patients with MCI. Here, we investigated whether epigenetic dysregulation in MCI and whether such an aberration could be detected in blood circulation. Genome-wide bisulfite sequencing targeted 84 million bases covering 3.7 million CpG sites was comparatively analyzed in MCI and control groups. And correlation between DNA methylation and transcriptomic changes was sought. Significant differentially methylated regions (DMRs) distinguishing the MCI and control groups were identified and functionally annotated. Most DMRs specific to MCI were enriched between – 2 kb and + 2 kb of the CpG island start sites located within or near gene promoters. Representative hypo- and hypermethylated DMRs in MCI were confirmed to be correlated to mRNA expression changes with the comparative delta Ct method. DNA methylation aberrations involving metal ion homeostasis, axon growth, inflammasome, and others in this study may be less-invasive, easily measurable blood biomarker candidates for MCI.

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Acknowledgements

The authors give special thanks to S.Y. Han and S. J. Song for assistance in the management of subjects.

Funding

This study was supported by Small and Medium Business Administration of South Korea (Grant No. S2261274).

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Correspondence to Sang Joon Son.

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The authors declare that they have no conflicts of interest.

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Park, MK., Lee, JW., Lee, JC. et al. NLRP1 and NTN1, Deregulated Blood Differentially Methylated Regions in Mild Cognitive Impairment Patients. J Mol Neurosci 66, 561–571 (2018). https://doi.org/10.1007/s12031-018-1180-5

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  • DOI: https://doi.org/10.1007/s12031-018-1180-5

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