Abstract
DNA methylation differences in Alzheimer's disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such as MAMSTR, AGAP2, and AZU1. The most significant DMR identified is located on the MAMSTR gene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.
Publication types
-
Meta-Analysis
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Aged
-
Aged, 80 and over
-
Alzheimer Disease / genetics*
-
Alzheimer Disease / immunology
-
Alzheimer Disease / metabolism*
-
Brain
-
Carrier Proteins / genetics
-
DNA Methylation / physiology*
-
Epigenesis, Genetic / genetics*
-
Epigenesis, Genetic / physiology
-
Female
-
GTP-Binding Proteins / genetics
-
GTPase-Activating Proteins / genetics
-
Gene Regulatory Networks
-
Genome-Wide Association Study
-
Humans
-
Immunity / genetics*
-
Immunity / physiology
-
MEF2 Transcription Factors / genetics
-
Prefrontal Cortex / physiology*
-
Transcription Factors / genetics
-
Tumor Suppressor Proteins / genetics
Substances
-
Carrier Proteins
-
GTPase-Activating Proteins
-
MEF2 Transcription Factors
-
MEF2C protein, human
-
TACC2 protein, human
-
Transcription Factors
-
Tumor Suppressor Proteins
-
AGAP2 protein, human
-
GTP-Binding Proteins