Methylation profiles in peripheral blood CD4+ lymphocytes versus brain: The relation to Alzheimer's disease pathology

Alzheimers Dement. 2016 Sep;12(9):942-951. doi: 10.1016/j.jalz.2016.02.009. Epub 2016 Mar 24.


Introduction: We investigated the change in DNA methylation in peripheral blood CD4+ lymphocytes over time, examined the relation between CD4+ lymphocytes and brain methylation, and compared their associations with AD pathology.

Methods: Genome-wide methylation was measured three times in 41 older persons using Illumina Infinium HumanMethylation450 array. The two CD4+ lymphocytes measures were at study baseline and proximate to death. Brain tissue came from frozen dorsolateral prefrontal cortex.

Results: Global methylation features were conserved across tissue. At individual CpG sites, methylation level was concordant between the two CD4+ lymphocytes but more diffuse between CD4+ lymphocytes and brain. Previous associations of brain methylation with neuritic plaques at target methylation sites were not replicated in CD4+ lymphocytes.

Discussion: There is no strong evidence of change in CD4+ lymphocytes methylation among older persons over an average of 7.5 years. Methylation associations with AD pathology found in neocortex are not directly reflected in CD4+ lymphocytes.

Keywords: Alzheimer's disease; CD4+ lymphocytes; DNA methylation; Dorsolateral prefrontal cortex.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / metabolism*
  • Chromatin / metabolism
  • Cohort Studies
  • DNA Methylation*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology*
  • White People


  • Biomarkers
  • Chromatin