N6-methyladenine-modified DNA was decreased in Alzheimer's disease patients
Shuang Lv1, Xiao Zhou2, Yi-Ming Li3
1Department of Neurology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China.
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.
Insights
N6-methyladenine (m6A) DNA levels are reduced in Alzheimer
Area of Science:
- Epigenetics and Neurodegenerative Diseases
- Biomarker Discovery in Alzheimer's Disease
- Molecular Mechanisms of Cognitive Decline
Background:
- Alzheimer's disease (AD) prevalence is rising, posing significant societal and healthcare challenges.
- N6-methyladenine (m6A) DNA adenine methylation is a novel biomarker, abundant in the brain but less common in AD.
- Investigating the role of DNA m6A in AD pathogenesis is crucial for understanding cognitive decline.
Purpose of the Study:
- To analyze the relationship between novel m6A DNA and cognitive function in Chinese patients with AD and normal controls (NCs).
- To determine if m6A DNA levels differ between AD patients and NCs.
- To explore correlations between m6A DNA levels, cognitive scores, and APOE ε4 status.
Main Methods:
- Included 179 AD patients and 147 age- and sex-matched NCs from China.
- Neuropsychological assessments, MRI, and APOE genotyping were performed.
- Global m6A DNA levels were quantified using ELISA and dot blotting, with PET imaging for validation.
Main Results:
- Global m6A DNA levels were significantly lower in AD patients compared to NCs (P = 0.002).
- Leukocyte m6A DNA levels were approximately 8.33% lower in AD patients.
- A significant positive correlation was observed between peripheral blood m6A levels and cognitive scores (r = 0.143, P = 0.01).
Conclusions:
- Reduced global m6A DNA methylation is significantly associated with Alzheimer's disease in the Chinese population.
- Lower m6A DNA levels may serve as a potential biomarker for AD.
- Further research is warranted to validate these findings and explore therapeutic implications.
Related Concept Videos
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:22Alzheimer's Disease: Treatment