Affiliations: [a] Institute of Nutrition & Health, Qingdao University, Qingdao, China
| [b] School of Public health, Qingdao University, Qingdao, China
| [c] Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| [d] Weifang Traditional Chinese Hospital, Weifang, China
Correspondence:
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Correspondence to: Prof. Qiuzhen Wang, Institute of Nutrition & Health, Qingdao University, Qingdao, China. Tel.: +86 532 85952895; Fax: +86 532 85952895; E-mail: kevin_1971@126.com.; Prof. Duo Li, Institute of Nutrition & Health, Qingdao University, Qingdao, China. Tel.: +86 532 82991018; Fax: +86 532 82991018; E-mail: duoli@qdu.edu.cn.
Abstract: Background:5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in central nervous system. It has been reported that DNA 5hmC dysregulation play a critical role in Alzheimer’s disease (AD) pathology. Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. Objective:However, the genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD has not been reported to date. Methods:We carried out a case-control study and used a genome-wide chemical capture followed by high-throughput sequencing to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in late-onset AD patients and the control. Results:We discovered significant differences of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls, indicating they can be well distinguished from normal controls by DhMRs in cfDNA. Specially, we identified 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) with predicting diagnostic potential based on their significant correlations with MMSE and MoCA scores of subjects. Conclusion:The present results suggest that 5hmC markers derived from plasma cfDNA can served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD.
