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Lookup NU author(s): Professor Alan ThomasORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022. The Author(s). Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2, SFMBT2, AKAP6 and PHYHIP. Differentially methylated probes were independent of known PD genetic risk alleles. Meta-analysis provided suggestive evidence for a differentially methylated locus within the chromosomal region affected by the PD-associated 22q11.2 deletion. Our findings elucidate novel disease pathways in PD and DLB and generate hypotheses for future molecular studies of Lewy body pathology.
Author(s): Pihlstrom L, Shireby G, Geut H, Henriksen SP, Rozemuller AJM, Tunold J-A, Hannon E, Francis P, Thomas AJ, Love S, Mill J, van de Berg WDJ, Toft M
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 22/08/2022
Acceptance date: 09/08/2022
Date deposited: 05/09/2022
ISSN (electronic): 2041-1723
Publisher: Springer Nature
PubMed id: 35995800
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