Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease

作者：Shaochang Wu, Fengtang Yang, Chao Shan, Bo Wang, Wuqian Wang, He Li, Limei Yu, Lin He, Xingwang Li, Liya Sun, Shengying Qin · 发表于：Frontiers in Genetics · 年份：2023 · DOI：10.3389/fgene.2023.1175864 · 被引用次数：10 · 研究领域：Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms、Tryptophan and brain disorders

Objective: DNA methylation plays a potential role in the pathogenesis of Alzheimer’s disease (AD). However, little is known about the global changes of blood leukocyte DNA methylome profiles from Chinese patients with mild cognitive impairment (MCI) and with AD, or the specific DNA methylation-based signatures associated with MCI and AD. In this study, we sought to dissect the characteristics of blood DNA methylome profiles in MCI- and AD-affected Chinese patients with the aim of identifying novel DNA methylation biomarkers for AD. Methods: In this study, we profiled the DNA methylome of peripheral blood leukocytes from 20 MCI- and 20 AD-affected Chinese patients and 20 cognitively healthy controls (CHCs) with the Infinium Methylation EPIC BeadChip array. Results: We identified significant alterations of the methylome profiles in MCI and AD blood leukocytes. A total of 2,582 and 20,829 CpG sites were significantly and differentially methylated in AD and MCI compared with CHCs (adjusted p < 0.05), respectively. Furthermore, 441 differentially methylated positions (DMPs), aligning to 213 unique genes, were overlapped by the three comparative groups of AD versus CHCs, MCI versus CHCs, and AD versus MCI, of which 6 and 5 DMPs were continuously hypermethylated and hypomethylated in MCI and AD relative to CHCs (adjusted p < 0.05), respectively, such as FLNC cg20186636 and AFAP1 cg06758191. The DMPs with an area under the curve >0.900, such as cg18771300, showed...