Importance
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.
Conclusion
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.