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The Role of Methylated Circulating Nucleic Acids as a Potential Biomarker in Alzheimer’s Disease

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Abstract

Previous studies report detection of high concentrations of circulating nucleic acids (CNAs), which are likely related to cell apoptosis, in the plasma of patients with cancers, stroke, trauma, and relapsing-remitting multiple sclerosis. However, the relationship between Alzheimer’s disease (AD) and CNAs is unclear. A total of 36 adult participants (9 non-demented controls and 27 patients with AD) and patients with mild AD, who met the criteria for probable AD, were enrolled in the present study, which was conducted at the Department of Neurology of National Cheng Kung University Hospital. The CNA levels were increased in the plasma of patients with AD, culture medium of amyloid-β-treated SH-SY5Y cells, and plasma from a mouse model of AD. The CNA concentrations in the plasma were positively correlated with the cognitive scores. Further, CNAs in patients with AD contained neuronal tissue-specific methylated LHX2, at CpG sites 1 and 5. These results showed that the increased levels of plasma CNAs could be related to neuronal cell death that was induced by β-amyloid toxicity. Thus, the results suggested that the levels of plasma CNAs and LHX2 methylation might serve as potential biomarkers for the diagnosis of AD, particularly during the early stages of the disease.

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Acknowledgements

The authors thank M.-T. Yu, C.-H. Pan, and Y.-T. Sun for their technical assistance in the study.

Abbreviations and Acronyms

CNAs, circulating nucleic acids; AD Alzheimer’s disease; LHX2, LIM homeobox 2 gene aCSF, artificial cerebrospinal fluid; CDR, Clinical Dementia Rating; MMSE, Mini-Mental State Examination; CASI, Cognitive Abilities Screening Instrument; MS, multiple sclerosis

Funding

This study was supported by grants from the NCKU Hospital Medical Center (NCKUH-10006002); Ministry of Health, Taiwan (DOH101-TD-B-111-0002); and Ministry of Science and Technology, Taiwan (MOST-104-2745-B-006-001, MOST-105-2628-B-006-016-MY3, and MOST-106-2628-B-006-001-MY4).

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Author notes

  1. Ming-Chyi Pai, Yu-Min Kuo and I-Fang Wang contributed equally to this work.

Authors and Affiliations

  1. Division of Behavioural Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ming-Chyi Pai

  2. Alzheimer’s Disease Research Centre, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ming-Chyi Pai, Yu-Min Kuo & Kuen-Jer Tsai

  3. Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yu-Min Kuo

  4. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan

    I-Fang Wang, Po-Min Chiang & Kuen-Jer Tsai

  5. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

    I-Fang Wang

  6. Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Kuen-Jer Tsai

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  1. Ming-Chyi Pai
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Contributions

K.-J. Tsai, Y.-M. Kuo, and M.-C. Pai contributed substantially to the conception and design of the research project and its scientific interpretation; K.-J. Tsai wrote the manuscript; I.-F. Wang and P.-M. Chiang took responsibility for the statistical analysis and reporting of the results.

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Correspondence to Kuen-Jer Tsai.

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Pai, MC., Kuo, YM., Wang, IF. et al. The Role of Methylated Circulating Nucleic Acids as a Potential Biomarker in Alzheimer’s Disease. Mol Neurobiol 56, 2440–2449 (2019). https://doi.org/10.1007/s12035-018-1229-z

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  • DOI: https://doi.org/10.1007/s12035-018-1229-z

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