Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain
Open accessAbstract
Epigenetic processes play a key role in the central nervous system and altered levels of 5-methylcytosine have been associated with a number of neurologic phenotypes, including Alzheimer's disease (AD). Recently, 3 additional cytosine modifications have been identified (5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine), which are thought to be intermediate steps in the demethylation of 5-methylcytosine to unmodified cytosine. Little is known about the frequency of these modifications in the human brain during health or disease. In this study, we used immunofluorescence to confirm the presence of each modification in human brain and investigate their cross-tissue abundance in AD patients and elderly control samples. We identify a significant AD-associated decrease in global 5-hydroxymethylcytosine in entorhinal cortex and cerebellum, and differences in 5-formylcytosine levels between brain regions. Our study further implicates a role for epigenetic alterations in AD.
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Age-dependent DNA methylation that occur in the brain are associated with the risk of developing various neurological diseases, including AD.
“Age-dependent DNA methylation that occur in the brain are associated with the risk of developing various neurological diseases14, including AD15,16.”
From Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice (2021) · cites this paper as [16]
The Introduction says some hydroxymethylated CpG sites change with aging, and the Conclusions report reduced 5-hydroxymethylcytosine in AD brain. The paper does not establish that age-dependent methylation changes are associated with the risk of developing AD; it compares brain tissue from AD cases and elderly controls. (LLM, conf=0.86)
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References 31 · Cited by 131
Research works printed but not linked: 26
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- Authors
- Condliffe, D., Wong, A., Troakes, C., Proitsi, P., Patel, Y., Chouliaras, L., Fernandes, C., Cooper, J., Lovestone, S., Schalkwyk, L., Mill, J., & Lunnon, K.
- Affiliations
- King's College London (GB)
- Maastricht University Medical Centre (NL)
- University of Exeter (GB)
- Corresponding author
- Lunnon, Katie
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 35
- Issue
- 8
- Pages
- 1850-1854
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4066184
- OpenAlex
- W2126837205
- Cited by
- 131
- References
- 31
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 3 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 16 · 2017: 20 · 2016: 17 · 2015: 10 · 2014: 9
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Open Access at Essex (University of Essex) (acceptedVersion)
- Figshare (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by-nc-nd)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- a US National Institutes of Health (NIH) (AG036039)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- 5-hydroxymethylcytosine, 5-formylcytosine, 5-carboxylcytosine, DNA methylation, demethylation, epigenetics, Alzheimer's disease, brain regions, entorhinal cortex, cerebellum
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cytosine, Female, Fluorescent Antibody Technique, Humans, Ivermectin, Male, Methylation, Epigenesis, Genetic, 5-Methylcytosine
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