Title | 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Chen, L, Shen, Q, Xu, S, Yu, H, Pei, S, Zhang, Y, He, X, Wang, QZ, Li, D |
Journal | J Alzheimers Dis |
Volume | 85 |
Issue | 2 |
Pagination | 573-585 |
Date Published | 2022 |
ISSN | 1875-8908 |
Keywords | 5-Methylcytosine, Aged, Alzheimer Disease, Biomarkers, Case-Control Studies, Cell-Free Nucleic Acids, DNA Methylation, DNA, Neoplasm, Epigenesis, Genetic, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged |
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. |
DOI | 10.3233/JAD-215217 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 34864677 |