Abstract
ImportanceEpigenetic 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).ObjectiveTo systematically review studies investigating epigenetic marks in AD or PD.MethodsEleven 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.ResultsOf 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.ConclusionMany 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.
Highlights
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative disorders and are a major cause of disability and premature death among older people worldwide [1,2,3]
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 neurodegenerative diseases (ND)
Summary
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative disorders and are a major cause of disability and premature death among older people worldwide [1,2,3]. The causes of most cases of neurodegenerative diseases remain largely unknown. It has been accepted that there are several genetic causes that play a role in the development of these disorders, including chromosome aberrations and gene mutations [8, 9]. Environmental exposures have been suggested to play a crucial role in the etiological process of neurodegenerative diseases. Both AD and PD are thought to be caused by complicated interactions between genetic and environmental factors [10]. A large amount of the variance in the risk of developing neurodegenerative diseases remains to be explained
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