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

Lei Yu; Lori B Chibnik; Jingyun Yang; Cristin McCabe; Jishu Xu; Julie A Schneider; Philip L De Jager; David A Bennett

doi:10.1016/j.jalz.2016.02.009

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.

Authors

Lei Yu¹, Lori B Chibnik², Jingyun Yang³, Cristin McCabe⁴, Jishu Xu⁴, Julie A Schneider⁵, Philip L De Jager², David A Bennett³

Affiliations

¹ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. Electronic address: lei_yu@rush.edu.
² Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
³ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
⁴ Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁵ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.

Abstract

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

Substances

Biomarkers
Chromatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding