title: Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.
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.
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: J V
authors.initials: JV
authors.lastname: Sanchez-Mut
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Heyn
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vidal
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Moran
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Sayols
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Delgado-Morales
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.|Bioinformatics Program, University of California at San Diego, La Jolla, CA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Schultz
authors.affiliation: Neuropathology Institute, Bellvitge Biomedical Research Institute-Hospital Universitari de Bellvitge, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Ansoleaga
authors.affiliation: Neuropathology Institute, Bellvitge Biomedical Research Institute-Hospital Universitari de Bellvitge, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Garcia-Esparcia
authors.affiliation: Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pons-Espinal
authors.affiliation: Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
authors.forename: M M
authors.initials: MM
authors.lastname: de Lagran
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Neuropathology Laboratory, Research Unit Alzheimer's Project, Fundación CIEN, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rabano
authors.affiliation: Department of Neuroscience, Centro de Biología Molecular Severo Ochoa CSIC/UAM, Universidad Autónoma de Madrid, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Avila
authors.affiliation: Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Dierssen
authors.affiliation: Department of Pediatrics and Neurology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Lott
authors.affiliation: Neuropathology Institute, Bellvitge Biomedical Research Institute-Hospital Universitari de Bellvitge, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.|Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Ecker
authors.affiliation: Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000502:physiology*; D057890:Epigenomics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D046888:Tissue Array Analysis