N6-methyladenine-modified DNA was decreased in Alzheimer’s disease patients

doi:10.12998/wjcc.v10.i2.448

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World Journal of Clinical Cases

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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.

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
Processing time: 186 Days and 14.4 Hours

ARTICLE HIGHLIGHTS

Research background

Alzheimer’s disease (AD) is the most common form of dementia and places a large burden on both society and family members. Extracellular senile plaques composed of amyloid-beta (Aβ) peptide and intracellular tau-containing neurofibrillary tangles in the brain are the classical view of AD pathogenesis.

Research motivation

Currently, targeting Aβ and tau-containing neurofibrillary tangles fails to stop the progression of AD. Studies have shown that early diagnosis and treatment are beneficial for improving the prognosis of AD patients. Thus, it is important to identify AD biomarkers.

Research objectives

This study aimed to determine the relationship between the novel m6A DNA and cognition in patients with AD and normal controls (NCs) in China. Complete the biomarkers of AD in clinical.

Research methods

The study included 179 AD patients and 147 NCs who were age- and sex-matched. All of them underwent neuropsychological scale assessment and magnetic resonance imaging examination. Blood samples were obtained from each subject to analyze apolipoprotein E (APOE) genotypes and global m6A levels. Global m6A levels were evaluated by a MethylFlash m6A DNA ELISA Kit (colorimetric). In addition, m6A levels 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.

Research results

The study showed that the m6A level was approximately 8.33% lower in AD patients than in NCs. Multivariate regression analysis further confirmed that the m6A level had a positive correlation with the occurrence of AD (P ≤ 0.01). The correlation between the MoCA score and peripheral blood m6A levels revealed that there was a significant correlation between the two in the tested population (r = 0.143, P = 0.01; < 0.05). However, m6A levels were not associated with APOE.

Research conclusions

The study showed that leukocyte m6A DNA levels are associated with AD and MoCA scores. Global m6A DNA methylation levels are significantly lower in AD patients than in NCs.

Research perspectives

We will further analyze the correlation between the m6A level and various aspects of cognition, such as memory and executive function. A further study will be performed to elucidate the effect of the m6A level on the pathological mechanisms of AD.