Lower DNA methylation levels in CpG island shores of CR1, CLU, and PICALM in the blood of Japanese Alzheimer’s disease patients
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Abstract
The aim of the present study was to (1) investigate the relationship between late-onset Alzheimer's disease (AD) and DNA methylation levels in six of the top seven AD-associated genes identified through a meta-analysis of recent genome wide association studies, APOE, BIN1, PICALM, CR1, CLU, and ABCA7, in blood, and (2) examine its applicability to the diagnosis of AD. We examined methylation differences at CpG island shores in the six genes using Sanger sequencing, and one of two groups of 48 AD patients and 48 elderly controls was used for a test or replication analysis. We found that methylation levels in three out of the six genes, CR1, CLU, and PICALM, were significantly lower in AD subjects. The combination of CLU methylation levels and the APOE genotype classified AD patients with AUC = 0.84 and 0.80 in the test and replication analyses, respectively. Our study implicates methylation differences at the CpG island shores of AD-associated genes in the onset of AD and suggests their diagnostic value.
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DNA methylation alterations can be detected in the blood of AD subjects.
“and can also be detected in the blood of AD subjects [25–31].”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [31]
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Braune, M., Metelmann, M., de Fallois, J., Pfrepper, C., Barrantes‐Freer, A., Hiller, G. G. R., Unger, S., Seelow, E., Halbritter, J., & Pelz, J. O. (2024) · Neurological Research and Practice · doi:10.1186/s42466-024-00327-2 · Cited by 1 · see citing works
Epigenetic Signatures of Aging: A Comprehensive Study of Biomarker Discovery
Lee, M. S., Kwon, H., Kim, Y., Min, N. Y., Lee, S. Y., & Lee, I. K. (2023) · Advances in Aging Research · doi:10.4236/aar.2023.122002 · Cited by 1 · see citing works
Nuytemans, K., Vasquez, M. L., Wang, L., Booven, D. V., Griswold, A. J., Rajabli, F., Celis, K., Oron, O., Hofmann, N. K., Rolati, S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.23.457375 · Cited by 1 · see citing works
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Additional file 2 of Distinct sex-specific DNA methylation differences in Alzheimer’s disease
Silva, T. C., Zhang, W. Y., Young, J. I., Gomez, L., Schmidt, M. A., Varma, A., Chen, X. S., Martin, E. R., & Wang, L. (2022) · Figshare · doi:10.6084/m9.figshare.21129954
Aryana-bs: context-aware alignment of bisulfite-sequencing reads
Nikaein, H., Sharifi‐Zarchi, A., Afzal, A., Ezzati, S., Rasti, F., Chitsaz, H., & Kunde‐Ramamoorthy, G. (2025) · BMC Bioinformatics · doi:10.1186/s12859-025-06182-5
Additional file 1 of Distinct sex-specific DNA methylation differences in Alzheimer’s disease
C. Silva, T., Zhang, W., Young, J. I., Gomez, L., Schmidt, M. A., Varma, A., Chen, X. S., Martin, E. R., & Wang, L. (2022) · Figshare · doi:10.6084/m9.figshare.21129953
Shimoda, N. (2026) · Epigenomics · doi:10.1080/17501911.2026.2635932
Self-citation
- Authors
- Mitsumori, R., Sakaguchi, K., Shigemizu, D., Mori, T., Akiyama, S., Ozaki, K., Niida, S., & Shimoda, N.
- Affiliations
- Medical Genome Center, National Center for Geriatrics and Gerontology (JP)
- National Center for Geriatrics and Gerontology (JP)
- Corresponding author
- Shimoda, Nobuyoshi
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-09-29
- Volume
- 15
- Issue
- 9
- Pages
- e0239196
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC7523949
- OpenAlex
- W3091154116
- Cited by
- 34
- References
- 59
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 3
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute for Geriatrics and Gerontology (26-16 and 29-20, 29-45)
- the Japanese Ministry of Health, Labor, and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, DNA methylation, CpG island shores, complement receptor 1, clusterin, PICALM, apolipoprotein E, blood biomarkers, Alzheimer's disease diagnosis, epigenetics, late-onset Alzheimer's disease, Japanese patients
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Japan, Male, Middle Aged, Biomarkers, Receptors, Complement 3b, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, Monomeric Clathrin Assembly Proteins, Clusterin, Genetic Association Studies
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