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Cited by 144Epigenetics and DNA MethylationAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

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Sanchez-Mut, Jose V., Aso, Ester, Panayotis, Nicolas, Lott, Ira, Dierssen, Mara, Rabano, Alberto, Urdinguio, Rocio G., Fernandez, Agustin F. +11 more·2013·Brain
DOI 10.1093/brain/awt237PMC PMC3784285
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Abstract

The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional activity, and aberrations in the distribution of this epigenetic mark may be involved in many neurological disorders, such as Alzheimer's disease. Herein, we have analysed 12 distinct mouse brain regions according to their CpG 5'-end gene methylation patterns and observed their unique epigenetic landscapes. The DNA methylomes obtained from the cerebral cortex were used to identify aberrant DNA methylation changes that occurred in two mouse models of Alzheimer's disease. We were able to translate these findings to patients with Alzheimer's disease, identifying DNA methylation-associated silencing of three targets genes: thromboxane A2 receptor (TBXA2R), sorbin and SH3 domain containing 3 (SORBS3) and spectrin beta 4 (SPTBN4). These hypermethylation targets indicate that the cyclic AMP response element-binding protein (CREB) activation pathway and the axon initial segment could contribute to the disease.

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  • Unbiased, genome-wide DNA methylation analyses have been used successfully to identify disease pathways in AD over-expressor models.

    “Unbiased, genome-wide DNA methylation analyses have been used successfully to identify disease pathways in AD over-expressor models22.”

    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 [22]

    The Results and Discussion report methylation changes in two transgenic Alzheimer’s mouse models and suggest links to CREB signalling and the axon initial segment. However, the Methods describe an array restricted to 384 selected genes, and the Discussion explicitly acknowledges that this selection biases the candidates. Calling the analysis “unbiased, genome-wide” therefore overstates what the paper did. (LLM, conf=0.91)

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Authors
Sanchez-Mut, J. V., Aso, E., Panayotis, N., Lott, I., Dierssen, M., Rabano, A., Urdinguio, R. G., Fernandez, A. F., Astudillo, A., Martin-Subero, J. I., Balint, B., Fraga, M. F., Gomez, A., Gurnot, C., Roux, J.-C., Avila, J., Hensch, T. K., Ferrer, I., & Esteller, M.
Affiliations
  • Institut d'Investigació Biomédica de Bellvitge (ES)
  • Bellvitge University Hospital (ES)
  • Inserm (FR)
  • University of California, Irvine (US)
  • Universitat Pompeu Fabra (ES)
  • Universidad de Oviedo (ES)
  • Harvard University (US)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
Corresponding author
Esteller, Manel
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2013-10
Volume
136
Issue
10
Pages
3018-3027
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awt237
PMC
PMC3784285
OpenAlex
W2132582013
Cited by
144
References
8
Citations by year
2026: 4 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 11 · 2018: 16 · 2017: 19 · 2016: 14 · 2015: 16 · 2014: 17
FWCI
7.02
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Brain (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by-nc)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • European Commission (278486)
  • National Institutes of Health
  • National Institute on Aging (P50 AG 16573, P50AG016573)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065160, HD065160-01)
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
DNA methylation, Alzheimer's disease, epigenetics, cerebral cortex, CpG methylation, mouse models of Alzheimer's disease, gene silencing, thromboxane A2 receptor, CREB signaling, axon initial segment, brain region-specific gene expression
MeSH terms
Alzheimer Disease, Animals, Brain, DNA, Humans, Mice, Inbred C57BL, Promoter Regions, Genetic, Gene Expression, Cyclic AMP Response Element-Binding Protein, DNA Methylation, Epigenesis, Genetic, Mice

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