DNA methylation analysis of candidate genes associated with dementia in peripheral blood

Peter D. Fransquet, Paul Lacaze, Richard Saffery, James Phung, Emily Parker, Raj C. Shah, Anne Murray, Robyn L. Woods, Joanne Ryan

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Aim: To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Materials & methods: Participants included 160 cognitively healthy individuals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood samples at diagnosis. Blood DNA methylation of APOE, APP, BDNF, PIN1, SNCA and TOMM40 was examined. Results: A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in APP (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis; cg19933173, Δ-4.18%, adjusted p < 0.0001 prediagnosis). Conclusion: Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.

Original languageEnglish
Pages (from-to)2109-2123
Number of pages15
JournalEpigenomics
Volume12
Issue number23
DOIs
Publication statusPublished - Dec 2020

Keywords

  • APOE
  • APP
  • BDNF
  • biomarker
  • blood
  • dementia
  • DNA methylation
  • PIN1
  • SNCA
  • TOMM40

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