{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:12:29Z","timestamp":1788667949156,"version":"build-2803163510"},"reference-count":47,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,1,18]]},"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3233\/jad-215217","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T16:56:46Z","timestamp":1638291406000},"page":"573-585","source":"Crossref","is-referenced-by-count":38,"title":["5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"85","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunliang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Weifang Traditional Chinese Hospital, Weifang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Pei","sequence":"additional","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"QiuZhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Nutrition & Health, Qingdao University, Qingdao, China"},{"name":"School of Public health, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-215217_ref1","doi-asserted-by":"crossref","unstructured":"(2020) 2020 Alzheimer\u2019s disease facts and figures. 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