APOE DNA methylation is altered in Lewy body dementia

Jessica Tulloch, Lesley Leong, Sunny Chen, C. Dirk Keene, Steven P. Millard, Andrew Shutes-David, Oscar L. Lopez, Julia Kofler, Jeffrey Kaye, Randall (Randy) Woltjer, Peter T. Nelson, Janna H. Neltner, Gregory A. Jicha, Douglas Galasko, Eliezer Masliah, James B. Leverenz, Chang En Yu, Debby Tsuang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Introduction: Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD. Methods: Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced. DNA methylation levels of two APOE subregions were then compared for these groups. Results: APOE DNA methylation was significantly reduced in npLBD compared with np controls, and methylation levels were lowest in the LBD + AD group. Discussion: Given that npLBD and npAD postmortem brains shared a similar reduction in APOE methylation, it is possible that an aberrant epigenetic change in APOE is linked to risk for both diseases.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Alzheimer's disease (AD)
  • Apolipoprotein E (APOE)
  • Cerebellum
  • Dementia with Lewy bodies (DLB)
  • Differential methylation
  • Differentially methylated region (DMR)
  • DNA methylation
  • Epigenetics
  • Frontal lobe
  • Human
  • Lewy body dementia (LBD)
  • Postmortem brain
  • Pyrosequencing

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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  • Cite this

    Tulloch, J., Leong, L., Chen, S., Keene, C. D., Millard, S. P., Shutes-David, A., Lopez, O. L., Kofler, J., Kaye, J., Woltjer, R. R., Nelson, P. T., Neltner, J. H., Jicha, G. A., Galasko, D., Masliah, E., Leverenz, J. B., Yu, C. E., & Tsuang, D. (Accepted/In press). APOE DNA methylation is altered in Lewy body dementia. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2018.02.005