Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease
Year: 2020
Type: review
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.
Source: Nature Communications
Institutions: University of Miami, Sylvester Comprehensive Cancer Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Awards: G1282666458, G1307745024, Building blood based DNA methylation signatures for AD that are reflective of CNS changes, G1457384572, G199972683, G2200385677, G249615658, G268727528, Exploring the Role of the Brain Transcriptome in Cognitive Decline, G3743240706, Pathway discovery, validation and compound identification for Alzheimer's disease, G3875713073, G4298697694, G4356727394, G5018538604, G5018925220, Alzheimer's Disease Genetics Consortium, G541333419, G5431283673, G5631886291, G5713958695, G5775146670, G578809140, G5952929075, G6084671875, G7396503879, G7479973302, G7906889984, G828200374, G860030259, Integrative Genomic Approaches for Understanding Sex Differences in Alzheimer's Disease, G8902171470, New statistical strategies for comprehensive analysis of epigenomewide methylation data, G9000015626, G9000066501, G9000088118, G9000099765, G9000110979, G9000244657, G983864884
OpenAlex ID: W3107160482