Epigenetic regulation of microglial gene expression in Alzheimer's disease

Neuroinflammation is emerging as a key pathogenetic event in risk and progression of Alzheimer's disease (AD). GWAS have identified single nucleotide polymorphisms (SNPs) at genetic loci associated with microglia function enriched in AD cohorts, however how these alter gene expression within loci is often unclear. Profiling transcriptional

regulation of AD associated gene by epigenome wide association studies of post-mortem human cortex has identified enriched patterns of DNA methylation in microglial genes of AD patients. Whilst further illuminating the contribution of microglia in AD pathogenesis, a caveat of these experiments is the tissue utilised; post-mortem samples of mixed

cell types derived from patients dying with late-stage AD with profound neurodegeneration and inflammation. Such tissues may not capture more subtle, early changes in epigenomic regulation that underpin functional changes in cells in prodromal patients.