Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential

Xiaojian Shao*, Sangeetha Vishweswaraiah, Miroslava Čuperlović-Culf, Ali Yilmaz, Celia M.T. Greenwood, Anuradha Surendra, Bernadette McGuinness, Peter Passmore, Patrick G. Kehoe, Michael E. Maddens, Steffany A.L. Bennett, Brian D. Green, Uppala Radhakrishna, Stewart F. Graham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Abstract

Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measure genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compare them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identify 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to “Parkinson’s disease” and “metabolic pathway”, as well as the diseases of “severe intellectual disability” and “mood disorders”. Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future.

Original languageEnglish
Article number1279
Number of pages11
JournalCommunications Biology
Volume5
Early online date22 Nov 2022
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
X.S. and M. C. are supported by the National Research Council Canada through the Aging in Place Challenge Program. This work was partly funded by the generous contribution made by the John and Marilyn Bishop Charitable Foundation and the Fred A. & Barbara M. Erb Foundation. S.F.G.’s laboratory is supported by grants from the National Institute of Neurological Disorders and Stroke (1R01NS110838- 01A1), the National Institute on Aging (1R21AG067083-01) and the Michael J. Fox Foundation (MJFF16201). B.D.G.’s laboratory has received support for AD research from Alzheimer’s Research UK (ARUK-NC2019-NI), the Medical Research Council (MRC) (CIC-CD1718-CIC25), US-Ireland Health and Social Care NI (HSC R&DST/5460/2018) and InvestNI (RD101427 11-01-17-008).

Funding Information:
X.S. and M. C. are supported by the National Research Council Canada through the Aging in Place Challenge Program. This work was partly funded by the generous contribution made by the John and Marilyn Bishop Charitable Foundation and the Fred A. & Barbara M. Erb Foundation. S.F.G.’s laboratory is supported by grants from the National Institute of Neurological Disorders and Stroke (1R01NS110838- 01A1), the National Institute on Aging (1R21AG067083-01) and the Michael J. Fox Foundation (MJFF16201). B.D.G.’s laboratory has received support for AD research from Alzheimer’s Research UK (ARUK-NC2019-NI), the Medical Research Council (MRC) (CIC-CD1718-CIC25), US-Ireland Health and Social Care NI (HSC R&DST/5460/2018) and InvestNI (RD101427 11-01-17-008).

Publisher Copyright:
© 2022, Crown.

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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