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Transl Psychiatry. 2016 Jan 19;6:e718. doi: 10.1038/tp.2015.214.

Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.

Author information

1
Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
2
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
3
Bioinformatics Program, University of California at San Diego, La Jolla, CA, USA.
4
Neuropathology Institute, Bellvitge Biomedical Research Institute-Hospital Universitari de Bellvitge, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Barcelona, Spain.
5
Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.
6
Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
7
Computational Genomics Department, Centro de Investigación Príncipe Felipe, Valencia, Spain.
8
Neuropathology Laboratory, Research Unit Alzheimer's Project, Fundación CIEN, Madrid, Spain.
9
Department of Neuroscience, Centro de Biología Molecular Severo Ochoa CSIC/UAM, Universidad Autónoma de Madrid, Madrid, Spain.
10
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain.
11
Department of Pediatrics and Neurology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
12
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.
13
Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain.
14
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

Abstract

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.

PMID:
26784972
PMCID:
PMC5068885
DOI:
10.1038/tp.2015.214
[Indexed for MEDLINE]
Free PMC Article

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