1. 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer's Disease.
- Author
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Chen L, Shen Q, Xu S, Yu H, Pei S, Zhang Y, He X, Wang Q, and Li D
- Subjects
- 5-Methylcytosine metabolism, Aged, Alzheimer Disease genetics, Alzheimer Disease pathology, Biomarkers metabolism, Case-Control Studies, DNA, Neoplasm metabolism, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, 5-Methylcytosine analogs & derivatives, Alzheimer Disease diagnosis, Cell-Free Nucleic Acids metabolism, DNA Methylation, Epigenesis, Genetic
- 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.
- Published
- 2022
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