An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene

Neurobiol Aging. 2020 Nov;95:26-45. doi: 10.1016/j.neurobiolaging.2020.06.023. Epub 2020 Jul 3.

Abstract

A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the AddNeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage.

Keywords: Alzheimer's disease (AD); Biomarker; Blood; DNA methylation; HOXB6; Mild cognitive impairment (MCI).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics
  • Brain / metabolism
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / genetics
  • DNA Methylation / genetics*
  • Female
  • Genome-Wide Association Study / methods*
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Male

Substances

  • Apolipoproteins E
  • HOXB6 protein, human
  • Homeodomain Proteins