Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease
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...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1175864/full |
| _version_ | 1827926622421909504 |
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| author | Shaochang Wu Fan Yang Fan Yang Fan Yang Shan Chao Bo Wang Bo Wang Wuqian Wang Wuqian Wang He Li Limei Yu Lin He Xingwang Li Liya Sun Liya Sun Liya Sun Shengying Qin |
| author_facet | Shaochang Wu Fan Yang Fan Yang Fan Yang Shan Chao Bo Wang Bo Wang Wuqian Wang Wuqian Wang He Li Limei Yu Lin He Xingwang Li Liya Sun Liya Sun Liya Sun Shengying Qin |
| author_sort | Shaochang Wu |
| collection | DOAJ |
| description | 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 high potency for predicting MCI and AD. In addition, gene ontology and pathway enrichment results showed that these overlapping genes were mainly involved in neurotransmitter transport, GABAergic synaptic transmission, signal release from synapse, neurotransmitter secretion, and the regulation of neurotransmitter levels. Furthermore, tissue expression enrichment analysis revealed a subset of potentially cerebral cortex-enriched genes associated with MCI and AD, including SYT7, SYN3, and KCNT1.Conclusion: This study revealed a number of potential biomarkers for MCI and AD, also highlighted the presence of epigenetically dysregulated gene networks that may engage in the underlying pathological events resulting in the onset of cognitive impairment and AD progression. Collectively, this study provides prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course. |
| first_indexed | 2024-03-13T05:40:30Z |
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| id | doaj.art-4583d8015bc04b948a3516aa0e8348d8 |
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| language | English |
| last_indexed | 2024-03-13T05:40:30Z |
| publishDate | 2023-06-01 |
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| spelling | doaj.art-4583d8015bc04b948a3516aa0e8348d82023-06-14T04:28:47ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-06-011410.3389/fgene.2023.11758641175864Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s diseaseShaochang Wu0Fan Yang1Fan Yang2Fan Yang3Shan Chao4Bo Wang5Bo Wang6Wuqian Wang7Wuqian Wang8He Li9Limei Yu10Lin He11Xingwang Li12Liya Sun13Liya Sun14Liya Sun15Shengying Qin16Department of Geriatrics, Lishui Second People’s Hospital, Lishui, ChinaKey Laboratory of Cell Engineering in Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, ChinaResearch Center for Lin He Academician New Medicine, Institutes for Shanghai Pudong Decoding Life, Shanghai, ChinaResearch Center for Lin He Academician New Medicine, Institutes for Shanghai Pudong Decoding Life, Shanghai, ChinaResearch Center for Lin He Academician New Medicine, Institutes for Shanghai Pudong Decoding Life, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, ChinaResearch Center for Lin He Academician New Medicine, Institutes for Shanghai Pudong Decoding Life, Shanghai, ChinaDepartment of Geriatrics, Lishui Second People’s Hospital, Lishui, ChinaKey Laboratory of Cell Engineering in Guizhou Province, Affiliated Hospital of Zunyi Medical University, Zunyi, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, ChinaResearch Center for Lin He Academician New Medicine, Institutes for Shanghai Pudong Decoding Life, Shanghai, ChinaShanghai Mental Health Center, Editorial Office, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, ChinaObjective: 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 high potency for predicting MCI and AD. In addition, gene ontology and pathway enrichment results showed that these overlapping genes were mainly involved in neurotransmitter transport, GABAergic synaptic transmission, signal release from synapse, neurotransmitter secretion, and the regulation of neurotransmitter levels. Furthermore, tissue expression enrichment analysis revealed a subset of potentially cerebral cortex-enriched genes associated with MCI and AD, including SYT7, SYN3, and KCNT1.Conclusion: This study revealed a number of potential biomarkers for MCI and AD, also highlighted the presence of epigenetically dysregulated gene networks that may engage in the underlying pathological events resulting in the onset of cognitive impairment and AD progression. Collectively, this study provides prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.https://www.frontiersin.org/articles/10.3389/fgene.2023.1175864/fullmild cognitive impairmentAlzheimer’s diseaseblood DNA methylome profiledifferentially methylated CpG sitespotential biomarker |
| spellingShingle | Shaochang Wu Fan Yang Fan Yang Fan Yang Shan Chao Bo Wang Bo Wang Wuqian Wang Wuqian Wang He Li Limei Yu Lin He Xingwang Li Liya Sun Liya Sun Liya Sun Shengying Qin Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease Frontiers in Genetics mild cognitive impairment Alzheimer’s disease blood DNA methylome profile differentially methylated CpG sites potential biomarker |
| title | Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease |
| title_full | Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease |
| title_fullStr | Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease |
| title_full_unstemmed | Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease |
| title_short | Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease |
| title_sort | altered dna methylome profiles of blood leukocytes in chinese patients with mild cognitive impairment and alzheimer s disease |
| topic | mild cognitive impairment Alzheimer’s disease blood DNA methylome profile differentially methylated CpG sites potential biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1175864/full |
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