Age-Dependent Increment of Hydroxymethylation in the Brain Cortex in the Triple-Transgenic Mouse Model of Alzheimer's Disease
Abstract
Alzheimer's disease (AD) is a complex disorder whose etiology is associated with environmental and genetic factors. Recently there have been several attempts to analyze the role of epigenetic alterations in the origin and progression of this neurodegenerative condition. To evaluate the potential participation of the methylation status of the genome that may contribute to AD progression, we have studied the levels and distribution of the 5-methylcytosine and 5-hydroxymethylcytosine in different brain regions at different ages. We analyzed and quantified the immunosignal of these two epigenetic marks in young versus old wild-type mice and in the triple-transgenic mouse model of AD (3xTg-AD). The results show a decline in global 5-methylcytosine mark over time in all studied brain regions concomitant with a significant and widespread increase in 5-hydroxymethylcytosine mark in the aged transgenic mice in contrast to the age-matched controls. These differences in the methylation pattern of brain DNA in the 3xTg-AD that accumulates along age indicates abnormal formation of permissive chromatin structure associated with the increase in AD-related markers.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Region-specific changes in DNA methylation were reported in the brains of triple-transgenic mouse model of AD (3xTg-AD).
“Consistently, region-specific changes in DNA methylation were reported in the brains of triple-transgenic mouse model of AD (3xTg-AD)19.”
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 [19]
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602 · see citing works
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830 · see citing works
HDAC2 negatively regulates memory formation and synaptic plasticity
Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., et al. (2009) · Nature · doi:10.1038/nature07925 · Cited by 1,644 · see citing works
Faghihi, M. A., Modarresi, F., Khalil, A. M., Wood, D. E., Sahagan, B. G., Morgan, T. E., Finch, C. E., St. Laurent III, G., Kenny, P. J., & Wahlestedt, C. (2008) · Nature Medicine · doi:10.1038/nm1784 · Cited by 1,416 · see citing works
Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain
Guo, J. U., Su, Y., Zhong, C., Ming, G., & Song, H. (2011) · Cell · doi:10.1016/j.cell.2011.03.022 · Cited by 1,355 · see citing works
Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease
Oddo, S. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.08.012 · Cited by 980 · see citing works
MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system
Mellén, M., Ayata, P., Dewell, S., Kriaucionis, S., & Heintz, N. (2012) · Cell · doi:10.1016/j.cell.2012.11.022 · Cited by 943 · see citing works
5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging
Szulwach, K. E., Li, X., Li, Y., Song, C., Wu, H., Dai, Q., Irier, H. A., Upadhyay, A. K., Gearing, M., Levey, A. I., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2959 · Cited by 819 · see citing works
Animal models of Alzheimer's disease and frontotemporal dementia
Götz, J., & Ittner, L. M. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2420 · Cited by 676 · see citing works
Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidationPreprint
Wu, H., & Zhang, Y. (2011) · Genes & Development · doi:10.17615/800j-yk16 · Cited by 665 · see citing works
Tau promotes neurodegeneration through global chromatin relaxation
Frost, B., Hemberg, M., Lewis, J., & Feany, M. B. (2014) · Nature Neuroscience · doi:10.1038/nn.3639 · Cited by 519 · cited 1× · see citing works
“A recent report demonstrated that abnormal induction by oxidative stress and DNA damage of the hyperphosphorylated form of the tau protein promotes a generalized heterochromatin loss that causes the aberrant de-repression of many genes [24].”
Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease
Wang, S.-C., Oelze, B., & Schumacher, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002698 · Cited by 467 · see citing works
Chouliaras, L., Mastroeni, D., Delvaux, E., Grover, A., Kenis, G., Hof, P. R., Steinbusch, H. W. M., Coleman, P. D., Rutten, B. P. F., & van den Hove, D. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.021 · Cited by 422 · see citing works
Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain
Coppieters, N., Dieriks, B. V., Lill, C. L., Faull, R. L. M., Curtis, M. A., & Dragunow, M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.031 · Cited by 350 · see citing works
Mastroeni, D., McKee, A. C., Grover, A., Rogers, J., & Coleman, P. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006617 · Cited by 292 · see citing works
Bakulski, K. M., Dolinoy, D. C., Sartor, M. A., Paulson, H. L., Konen, J. R., Lieberman, A. P., Albin, R. L., Hu, H., & Rozek, L. S. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-111223 · Cited by 255 · see citing works
Complex disease, gender and epigenetics
Kaminsky, Z. A., Wang, S., & Petronis, A. (2006) · Annals of Medicine · doi:10.1080/07853890600989211 · Cited by 209 · see citing works
Epigenetic changes in the progression of Alzheimer's disease
Bradley‐Whitman, M. A., & Lovell, M. A. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.08.005 · Cited by 193 · see citing works
Genetic Factors in Alzheimer's Disease
Bird, T. D. (2005) · New England Journal of Medicine · doi:10.1056/nejmp058027 · Cited by 122 · see citing works
Dynamics of DNA Methylation in Aging and Alzheimer's Disease
Irier, H. A., & Jin, P. (2012) · DNA and Cell Biology · doi:10.1089/dna.2011.1565 · Cited by 84 · see citing works
Decoding the non-coding RNAs in Alzheimer’s disease
Schönrock, N., & Götz, J. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1125-z · Cited by 60 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Epigenetic Alterations in Alzheimer’s Disease
Sanchez-Mut, J. V., & Gräff, J. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00347 · Cited by 168 · see citing works
Salminen, A., Haapasalo, A., Kauppinen, A., Kaarniranta, K., Soininen, H. S., & Hiltunen, M. O. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.001 · Cited by 105 · see citing works
Schueller, E., Paiva, I., Blanc, F., Wang, X., Cassel, J., Boutillier, A., & Bousiges, O. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.01.015 · Cited by 91 · see citing works
Carmo, S. D., Hanzel, C. E., Jacobs, M. L., Machnes, Z. M., Iulita, M. F., Yang, J., Yu, L., Ducatenzeiler, A., Danik, M., Breuillaud, L., et al. (2016) · Scientific Reports · doi:10.1038/srep34051 · Cited by 79 · see citing works
Kundu, P., Torres, E. R. S., Stagaman, K., Kasschau, K., Okhovat, M., Holden, S., Ward, S., Nevonen, K. A., Davis, B. A., Saito, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-83851-4 · Cited by 75 · see citing works
Role of 5-hydroxymethylcytosine in neurodegeneration
Sherwani, S. I., & Khan, H. A. (2015) · Gene · doi:10.1016/j.gene.2015.06.052 · Cited by 70 · see citing works
Cao, T., Zhou, X., Zheng, X., Cui, Y., Tsien, J. Z., Li, C., & Wang, H. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00137 · Cited by 61 · see citing works
Antunes, C., Silva, J. D. D., Guerra‐Gomes, S., Alves, N. D., Ferreira, F., Loureiro‐Campos, E., Branco, M. R., Sousa, N., Reik, W., Pinto, L., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0695-7 · Cited by 60 · see citing works
Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer’s disease
Shu, L., Sun, W., Li, L., Xu, Z., Lin, L., Xie, P., Shen, H., Huang, L., Xu, Q., Jin, P., et al. (2016) · BMC Genomics · doi:10.1186/s12864-016-2731-1 · Cited by 59 · see citing works
Sharma, M., Dierkes, T., & Sajikumar, S. (2017) · Aging Cell · doi:10.1111/acel.12634 · Cited by 57 · see citing works
TET enzymes in neurophysiology and brain function
Antunes, C., Sousa, N., Pinto, L., & Marques, C. J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.006 · Cited by 55 · see citing works
Lardenoije, R., van den Hove, D., Havermans, M., van Casteren, A., Le, K. X., Palmour, R., Lemere, C. A., & Rutten, B. P. F. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.11.002 · Cited by 42 · see citing works
5-Hydroxymethylcytosine (5hmC), or How to Identify Your Favorite Cell
Ecsedi, S., Rodríguez‐Aguilera, J. R., & Hernández‐Vargas, H. (2018) · Epigenomes · doi:10.3390/epigenomes2010003 · Cited by 37 · see citing works
Epigenetic basis of Alzheimer disease
Tecalco-Cruz, Á. C., Ramírez‐Jarquín, J. O., Álvarez-Sánchez, M. E., & Zepeda–Cervantes, J. (2020) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v11.i2.62 · Cited by 37 · see citing works
Roig-Soriano, J., Griñán‐Ferré, C., Espinosa‐Parrilla, J. F., Abraham, C. R., Bosch, A., Pallàs, M., & Chillón, M. (2022) · Aging Cell · doi:10.1111/acel.13581 · Cited by 33 · see citing works
Role of TET1-mediated epigenetic modulation in Alzheimer's disease
Armstrong, M. J., Jin, Y., Vattathil, S., Huang, Y., Schroeder, J. P., Bennet, D. A., Qin, Z. S., Wingo, T. S., & Jin, P. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106257 · Cited by 30 · see citing works
DNA methylation dynamics underlie metamorphic gene regulation programs in Xenopus tadpole brain
Kyono, Y., Raj, S., Sifuentes, C. J., Buisine, N., Sachs, L. M., & Denver, R. J. (2020) · Developmental Biology · doi:10.1016/j.ydbio.2020.03.013 · Cited by 29 · see citing works
Clinical relevance of animal models in aging-related dementia research
Padmanabhan, P., & Götz, J. (2023) · Nature Aging · doi:10.1038/s43587-023-00402-4 · Cited by 28 · see citing works
Fertan, E., Wong, A. A., Vienneau, N. A., & Brown, R. E. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.111937 · Cited by 22 · see citing works
Experimental Pharmacology in Transgenic Rodent Models of Alzheimer’s Disease
Cuello, A. C., Hall, H., & Carmo, S. D. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00189 · Cited by 19 · see citing works
Song, F., Han, G., Bai, Z., Peng, X., Wang, J., & Lei, H. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.05.001 · Cited by 16 · see citing works
Zhang, Y., Zhang, Y., Chen, D., Wang, C., Chen, L., Gao, C., Fan, W. Q., Shi, J., Zhang, J., & Li, B. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00214 · Cited by 15 · see citing works
Epigenetic Studies in the Male APP/BIN1/COPS5 Triple-Transgenic Mouse Model of Alzheimer’s Disease
Martínez-Iglesias, O. A., Naidoo, V., Carrera, I., & Cacabelos, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052446 · Cited by 10 · see citing works
Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice
Chouliaras, L., Lardenoije, R., Kenis, G., Mastroeni, D., Hof, P. R., van Os, J., Steinbusch, H. W. M., van Leeuwen, F. W., Rutten, B. P. F., & van den Hove, D. (2018) · Translational Neuroscience · doi:10.1515/tnsci-2018-0028 · Cited by 10 · see citing works
Engrampigenetics: Epigenetics of engram memory cells
Ripoli, C. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.11.043 · Cited by 9 · see citing works
Epigenetic processes in Alzheimer's disease
Castanho, I., & Lunnon, K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813796-3.00008-0 · Cited by 9 · see citing works
The Neuroepigenetic Landscape of Vertebrate and Invertebrate Models of Neurodegenerative Diseases
Sundaramoorthy, T. H., & Castanho, I. (2022) · Epigenetics Insights · doi:10.1177/25168657221135848 · Cited by 6 · see citing works
DNA Methylation in Neuronal Development and Disease
Bruggeman, E. C., & Yao, B. (2019) · RNA technologies · doi:10.1007/978-3-030-14792-1_5 · Cited by 6 · see citing works
5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues
Hernaiz, A., Sentre, S., Betancor, M., López-Pérez, Ó., Salinas‐Pena, M., Zaragoza, P., Badiola, J. J., Toivonen, J. M., Bolea, R., & Martín‐Burriel, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021621 · Cited by 5 · see citing works
Yang, T., Wei, Q., Pang, D., Cheng, Y., Huang, J., Lin, J., Xiao, Y., Jiang, Q., Wang, S., Li, C., et al. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12508-9 · Cited by 4 · see citing works
Fuso, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812215-0.00031-5 · Cited by 2 · see citing works
Fuso, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-21863-7.00016-0 · Cited by 1 · see citing works
Causal links between mitophagy and Alzheimer’s disease: a Mendelian randomization studyPreprint
Zhang, W., Chen, W., Guo, Z., & Li, H. (2024) · medRxiv · doi:10.1101/2024.10.01.24314751 · Cited by 1 · see citing works
Turk, M., & Huentelman, M. J. (2015) · Personalized Medicine · doi:10.2217/pme.15.18
Tecalco-Cruz, Á. C., Macías‐Silva, M., Ramírez‐Jarquín, J. O., Ríos-López, D. G., & Zepeda–Cervantes, J. (2021) · TIP Revista Especializada en Ciencias Químico-Biológicas · doi:10.22201/fesz.23958723e.2021.0.295
- Authors
- Cadena-del-Castillo, C., Valdes-Quezada, C., Carmona-Aldana, F., Arias, C., Bermúdez-Rattoni, F., & Recillas-Targa, F.
- Affiliations
- Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México
- Universidad Nacional Autónoma de México (MX)
- Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (MX)
- Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2014-07-16
- Volume
- 41
- Issue
- 3
- Pages
- 845-854
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1640694777
- Cited by
- 35
- References
- 23
- Citations by year
- 2024: 2 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 5
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- 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
- Alzheimer's disease, 5-hydroxymethylcytosine
- MeSH terms
- Age Factors, Aging, Alzheimer Disease, Animals, Cerebral Cortex, Cytosine, Disease Models, Animal, Gene Expression Regulation, Genotype, Humans, Methylation, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, 5-Methylcytosine, Mice, Presenilin-1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review