Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites
Abstract Objective Dementia, particularly Alzheimer’s disease (AD), continues to be a major public health concern due to population aging, yet minimally invasive biomarkers for early diagnosis have not been established. DNA methylation (DNAm) has recently attracted considerable attention as a promis...
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2025-08-01
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| Online Access: | https://doi.org/10.1186/s13104-025-07417-7 |
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| author | Hideki Ohmomo Shohei Komaki Shiori Minabe Yoichi Sutoh Yayoi Otsuka-Yamasaki Makoto Sasaki Atsushi Shimizu |
| author_facet | Hideki Ohmomo Shohei Komaki Shiori Minabe Yoichi Sutoh Yayoi Otsuka-Yamasaki Makoto Sasaki Atsushi Shimizu |
| author_sort | Hideki Ohmomo |
| collection | DOAJ |
| description | Abstract Objective Dementia, particularly Alzheimer’s disease (AD), continues to be a major public health concern due to population aging, yet minimally invasive biomarkers for early diagnosis have not been established. DNA methylation (DNAm) has recently attracted considerable attention as a promising biomarker. This study aimed to identify blood-based DNAm biomarkers for early detection of AD. Results We analysed blood-derived DNA from 48 patients with AD (from Biobank Japan) and 48 age- and sex-matched controls (from the Tohoku Medical Megabank Biobank) using Apolipoprotein ε type 4 (APOE)-associated genotype analysis and targeted-bisulfite sequencing. High-risk APOE genotypes were more frequent in AD patients (23/48, [47.9%]) than in controls (6/48, [12.5%]). A typical case-control and APOE genotype-stratified epigenome-wide association study (EWAS) did not identify any genome-wide significant CpG sites. Although the primary findings were negative, some top CpG sites appeared in both analyses, including loci on the Cell Adhesion Molecule 1 (CADM1), Tubulin alpha 1b (TUBA1B), and Exocyst complex component 2 (EXOC2) genes, which have previously been linked to AD-related pathways. The relatively early clinical stage and uncertainty of disease onset might have limited detection sensitivity. Longitudinal studies with refined staging and multi-omics integration might clarify the biomarker potential of blood DNAm in AD. |
| format | Article |
| id | doaj-art-92849d2b414b4299a86b5ddbcd1d917a |
| institution | Kabale University |
| issn | 1756-0500 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | BMC Research Notes |
| spelling | doaj-art-92849d2b414b4299a86b5ddbcd1d917a2025-08-20T03:45:44ZengBMCBMC Research Notes1756-05002025-08-011811710.1186/s13104-025-07417-7Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sitesHideki Ohmomo0Shohei Komaki1Shiori Minabe2Yoichi Sutoh3Yayoi Otsuka-Yamasaki4Makoto Sasaki5Atsushi Shimizu6Division of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical UniversityDivision of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical UniversityDivision of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical UniversityDivision of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical UniversityDivision of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical UniversityDisaster Reconstruction Center, Iwate Tohoku Medical Megabank Organization, Iwate Medical UniversityDivision of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical UniversityAbstract Objective Dementia, particularly Alzheimer’s disease (AD), continues to be a major public health concern due to population aging, yet minimally invasive biomarkers for early diagnosis have not been established. DNA methylation (DNAm) has recently attracted considerable attention as a promising biomarker. This study aimed to identify blood-based DNAm biomarkers for early detection of AD. Results We analysed blood-derived DNA from 48 patients with AD (from Biobank Japan) and 48 age- and sex-matched controls (from the Tohoku Medical Megabank Biobank) using Apolipoprotein ε type 4 (APOE)-associated genotype analysis and targeted-bisulfite sequencing. High-risk APOE genotypes were more frequent in AD patients (23/48, [47.9%]) than in controls (6/48, [12.5%]). A typical case-control and APOE genotype-stratified epigenome-wide association study (EWAS) did not identify any genome-wide significant CpG sites. Although the primary findings were negative, some top CpG sites appeared in both analyses, including loci on the Cell Adhesion Molecule 1 (CADM1), Tubulin alpha 1b (TUBA1B), and Exocyst complex component 2 (EXOC2) genes, which have previously been linked to AD-related pathways. The relatively early clinical stage and uncertainty of disease onset might have limited detection sensitivity. Longitudinal studies with refined staging and multi-omics integration might clarify the biomarker potential of blood DNAm in AD.https://doi.org/10.1186/s13104-025-07417-7Alzheimer’s diseaseDNA methylation biomarkersEpigenome-wide association studyTargeted-bisulphite sequencingAPOE genotyping |
| spellingShingle | Hideki Ohmomo Shohei Komaki Shiori Minabe Yoichi Sutoh Yayoi Otsuka-Yamasaki Makoto Sasaki Atsushi Shimizu Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites BMC Research Notes Alzheimer’s disease DNA methylation biomarkers Epigenome-wide association study Targeted-bisulphite sequencing APOE genotyping |
| title | Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites |
| title_full | Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites |
| title_fullStr | Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites |
| title_full_unstemmed | Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites |
| title_short | Exploring novel blood-based DNA methylation biomarkers for alzheimer’s disease via targeted sequencing of highly variable CpG sites |
| title_sort | exploring novel blood based dna methylation biomarkers for alzheimer s disease via targeted sequencing of highly variable cpg sites |
| topic | Alzheimer’s disease DNA methylation biomarkers Epigenome-wide association study Targeted-bisulphite sequencing APOE genotyping |
| url | https://doi.org/10.1186/s13104-025-07417-7 |
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