Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 14, 2022; 10(2): 448-457
Published online Jan 14, 2022. doi: 10.12998/wjcc.v10.i2.448
N6-methyladenine-modified DNA was decreased in Alzheimer’s disease patients
Shuang Lv, Xiao Zhou, Yi-Ming Li, Tao Yang, Shu-Juan Zhang, Yu Wang, Shu-Hong Jia, Dan-Tao Peng
Shuang Lv, Dan-Tao Peng, Department of Neurology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
Shuang Lv, Xiao Zhou, Shu-Juan Zhang, Yu Wang, Shu-Hong Jia, Dan-Tao Peng, Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
Xiao Zhou, Dan-Tao Peng, Department of Neurology, Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100029, China
Yi-Ming Li, Department of Cardiovascular, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Tao Yang, Department of Geriatric, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100039, China
Author contributions: Lv S and Zhou X contributed equally as co-first authors; Lv S and Zhou X performed the research and drafted the initial manuscript; Peng DT, Wang Y and Jia SH diagnosed the Alzheimer’s disease; Zhang SJ collected the data related to the study; Li YM analyzed the data related to the study; Yang T revised the manuscript and generated the figures; Peng DT was the guarantor and designed the study; all authors have read and approved the final manuscript.
Supported by the National Key R&D Program of China, No. 2016YFC1306300; and the National Natural Science Foundation of China, No. 81974220.
Institutional review board statement: The study was reviewed and approved by the China-Japan Friendship Hospital Institutional Review Board (Approval No. 2018-22-Y06).
Informed consent statement: Informed consent was obtained from patients in this study.
Conflict-of-interest statement: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data sharing statement: The data will not be publicly available because of privacy or ethical restrictions. The data will be partly available from the corresponding author.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dan-Tao Peng, PhD, Chief Physician, Professor, Department of Neurology, China-Japan Friendship Hospital, No. 2 Yinghuayuandong Street, Beijing 100029, China. pengdantao2000@163.com
Received: July 9, 2021
Peer-review started: July 9, 2021
First decision: November 11, 2021
Revised: November 11, 2021
Accepted: December 7, 2021
Article in press: December 7, 2021
Published online: January 14, 2022
Abstract
BACKGROUND

In recent years, the prevalence of Alzheimer’s disease (AD) has increased, which places a great burden on society and families and creates considerable challenges for medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA) adenine methylation is a novel biomarker and is abundant in the brain, but less common in AD. We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls (NCs) in China.

AIM

To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.

METHODS

A total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and 147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age- and sex-matched were included in our study. All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination. Apolipoprotein E (APOE) genotypes were measured through agarose gel electrophoresis. Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patients with 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.

RESULTS

Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs (P = 0.002; < 0.05). And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting. There were significant differences between the two groups, which indicated that the leukocyte m6A DNA levels were different (P = 0.005; < 0.05). The m6A level was approximately 8.33% lower in AD patients than in NCs (mean 0.011 ± 0.006 vs 0.012 ± 0.005). A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population (r = 0.143, P = 0.01; < 0.05). However, no relationship was found with APOE ε4 (P = 0.633, > 0.05). Further studies should be performed to validate these findings.

CONCLUSION

Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33% in China.

Keywords: Alzheimer disease, N6-methyladenine, DNA, Montreal Cognitive Assessment, Apolipoprotein E, Cognitive dysfunction

Core Tip: Although Alzheimer’s disease (AD) cannot be cured, early diagnosis and treatment can greatly improve the prognosis of AD patients. Thus, we aimed to identify biomarkers of AD that can be useful in the clinic. The diagnostic criteria for AD were strictly employed in the study. We found that N6-methyladenine (m6A) DNA adenine methylation may be a novel biomarker of AD. Twenty subjects underwent 18F-AV-45 (florbetapir) positron emission tomography to test this assertion. In addition, the global m6A DNA methylation level was also correlated with cognition level.