Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies

Paolo Reho, Sara Saez-Atienzar, Paola Ruffo, Sultana Solaiman, Zalak Shah, Ruth Chia, Karri Kaivola, Bryan J. Traynor, Bension S. Tilley, Steve M. Gentleman, Angela K. Hodges, Dag Aarsland, Edwin S. Monuki, Kathy L. Newell, Randy Woltjer, Marilyn S. Albert, Ted M. Dawson, Liana S. Rosenthal, Juan C. Troncoso, Olga PletnikovaGeidy E. Serrano, Thomas G. Beach, Hariharan P. Easwaran, Sonja W. Scholz

Research output: Contribution to journalArticlepeer-review

Abstract

Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly population. We performed genome-wide DNA methylation mapping of cerebellar tissue from pathologically confirmed DLB cases and controls to study the epigenetic profile of this understudied disease. After quality control filtering, 728,197 CpG-sites in 278 cases and 172 controls were available for the analysis. We undertook an epigenome-wide association study, which found a differential methylation signature in DLB cases. Our analysis identified seven differentially methylated probes and three regions associated with DLB. The most significant CpGs were located in ARSB (cg16086807), LINC00173 (cg18800161), and MGRN1 (cg16250093). Functional enrichment evaluations found widespread epigenetic dysregulation in genes associated with neuron-to-neuron synapse, postsynaptic specialization, postsynaptic density, and CTCF-mediated synaptic plasticity. In conclusion, our study highlights the potential importance of epigenetic alterations in the pathogenesis of DLB and provides insights into the modified genes, regions and pathways that may guide therapeutic developments.

Original languageEnglish (US)
Article number35
JournalCommunications biology
Volume7
Issue number1
DOIs
StatePublished - Dec 2024

ASJC Scopus subject areas

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

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