A Preliminary Comparison of the Methylome and Transcriptome from the Prefrontal Cortex Across Alzheimer's Disease and Lewy Body Dementia.

Background: Pathological amyloid-β and Objective: In this preliminary study, we explore differences in DNA methylation and transcription in five neuropathologically defined groups: cognitively unimpaired controls, AD, pure DLB, DLB with concomitant AD (DLBAD), and PDD. Methods: We employed an Illumina Infinium 850k array and RNA-seq to quantify these differences in DNA methylation and transcription, respectively. We then used Weighted Gene Co-Network Expression Analysis (WGCNA) to determine transcriptional modules and correlated these with DNA methylation. Results: We found that PDD was transcriptionally unique and correlated with an unexpected hypomethylation pattern compared to the other dementias and controls. Surprisingly, differences between PDD and DLB were especially notable with 197 differentially methylated regions. WGCNA yielded numerous modules associated with controls and the four dementias: one module was associated with transcriptional differences between controls and all the dementias as well as having significant overlap with differentially methylated probes. Functional enrichment demonstrated that this module was associated with responses to oxidative stress. Conclusion: Future work that extends these joint DNA methylation and transcription analyses will be critical to better understanding of differences that contribute to varying clinical presentation across dementias.