Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

被引:120
作者
Sanchez-Mut, J. V. [1 ]
Heyn, H. [1 ]
Vidal, E. [1 ]
Moran, S. [1 ]
Sayols, S. [1 ]
Delgado-Morales, R. [1 ]
Schultz, M. D. [2 ,3 ]
Ansoleaga, B. [4 ]
Garcia-Esparcia, P. [4 ]
Pons-Espinal, M. [5 ,6 ]
de lagran, M. M. [5 ,6 ]
Dopazo, J. [7 ]
Rabano, A. [8 ]
Avila, J. [9 ,10 ]
Dierssen, M. [5 ,6 ]
Lott, I. [11 ]
Ferrer, I. [4 ]
Ecker, J. R. [2 ,12 ]
Esteller, M. [1 ,13 ,14 ]
机构
[1] Bellvitge Biomed Res Inst, Epigenet & Biol Program, Ave Gran Via Km 2-7, Barcelona 08908, Spain
[2] Salk Inst Biol Studies, Genom Anal Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA
[4] Univ Barcelona, Hosp Univ Bellvitge, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Neuropathol Inst,Bellvitge Biomed Res Inst, Barcelona, Spain
[5] Univ Pompeu Fabra, Ctr Genom Regulat, Barcelona, Spain
[6] Ctr Invest Biomed Red Enfermedades Raras, Barcelona, Spain
[7] Ctr Invest Principe Felipe, Computat Genom Dept, Valencia, Spain
[8] Fdn CIEN, Res Unit Alzheimers Project, Neuropathol Lab, Madrid, Spain
[9] Univ Autonoma Madrid, Dept Neurosci, Ctr Biol Mol Severo Ochoa CSIC UAM, Madrid, Spain
[10] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
[11] Univ Calif Irvine, Sch Med, Dept Pediat & Neurol, Irvine, CA 92717 USA
[12] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA
[13] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Spain
[14] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain
关键词
DIFFERENTIALLY METHYLATED REGIONS; ALZHEIMERS-DISEASE; FRONTAL-CORTEX; MOUSE-BRAIN; GENOME; GENES; DEREGULATION; EXPRESSION; MODEL; ANK1;
D O I
10.1038/tp.2015.214
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
引用
收藏
页码:e718 / e718
页数:8
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