title: The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.
abstract: OBJECTIVE
  Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD).
  
  
  OBJECTIVE
  To systematically review studies investigating epigenetic marks in AD or PD.
  
  
  METHODS
  Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.
  
  
  RESULTS
  Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.
  
  
  CONCLUSIONS
  Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Wen
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Jelena
authors.initials: J
authors.lastname: Miliç
authors.affiliation: Research and Development, Metagenics, Inc, United States of America.
authors.forename: Bassem
authors.initials: B
authors.lastname: El-Khodor
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Klodian
authors.initials: K
authors.lastname: Dhana
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Jana
authors.initials: J
authors.lastname: Nano
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Tammy
authors.initials: T
authors.lastname: Pulido
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, University of Medicine, Tirana, Albania.|University Clinic of Gastrohepatology, University Hospital Center Mother Teresa, Tirana, Albania.
authors.forename: Bledar
authors.initials: B
authors.lastname: Kraja
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Asija
authors.initials: A
authors.lastname: Zaciragic
authors.affiliation: Medical Library, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Wichor M
authors.initials: WM
authors.lastname: Bramer
authors.affiliation: Research and Development, Metagenics, Inc, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Troup
authors.affiliation: Department of Public Health & Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, United Kingdom.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: M Arfam
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Taulant
authors.initials: T
authors.lastname: Muka
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D015982:Bias; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015894:Genome, Human; D042421:Histone Code; D006657:Histones / Q000737:chemistry*; D006801:Humans; D007249:Inflammation; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D006657:Histones