Associations of serum DNA methylation levels of chemokine signaling pathway genes with mild cognitive impairment (MCI) and Alzheimer's disease (AD)

PLoS One. 2023 Dec 1;18(12):e0295320. doi: 10.1371/journal.pone.0295320. eCollection 2023.

Abstract

Objective: To investigate the associations of serum DNA methylation levels of chemokine signaling pathway genes with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in elderly people in Xinjiang, China, and to screen out genes whose DNA methylation could distinguish AD and MCI.

Materials and methods: 37 AD, 40 MCI and 80 controls were included in the present study. DNA methylation assay was done using quantitative methylation-specific polymerase chain reaction (qMSP). Genotyping was done using Sanger sequencing.

Results: DNA methylation levels of ADCY2, MAP2K1 and AKT1 were significantly different among AD, MCI and controls. In the comparisons of each two groups, AKT1 and MAP2K1's methylation was both significantly different between AD and MCI (p < 0.05), whereas MAP2K1's methylation was also significantly different between MCI and controls. Therefore, AKT1's methylation was considered as the candidate serum marker to distinguish AD from MCI, and its association with AD was independent of APOE ε4 allele (p < 0.05). AKT1 hypermethylation was an independent risk factor for AD and MAP2K1 hypomethylation was an independent risk factor for MCI in logistic regression analysis (p < 0.05).

Conclusion: This study found that the serum of AKT1 hypermethylation is related to AD independently of APOE ε4, which was differentially expressed in the Entorhinal Cortex of the brain and was an independent risk factor for AD. It could be used as one of the candidate serum markers to distinguish AD and MCI. Serum of MAP2K1 hypomethylation is an independent risk factor for MCI.

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics
  • Chemokines / genetics
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / genetics
  • DNA Methylation
  • Humans
  • Signal Transduction / genetics

Substances

  • Apolipoprotein E4
  • Chemokines

Grants and funding

This research was supported by the grants from the National Natural Science Foundation of China (No. 81360064), which had role in study design, data collection. the Key project of Xinjiang Natural Science Foundation (No. 2022D01D63), which had role in decision to publish. National Key research and development program (2016YFC1305900), which were in charge of preparation of the manuscript in the study.