Abstract
AbstractRecent studies have demonstrated that the dorsal raphe nucleus (DRN) is among the first brain regions affected in Alzheimer’s disease. Hence, in this study we conducted the first comprehensive epigenetic analysis of the DRN in AD, targeting both bulk tissue and single isolated cells. The Illumina Infinium MethylationEPIC BeadChip array was used to analyze the bulk tissue, assessing differentially modified positions (DMoPs) and regions (DMoRs) associated with Braak stage. The strongest Braak stage-associated DMoR inTNXBwas targeted in a second patient cohort utilizing single laser-capture microdissected serotonin-positive (5-HT+) and -negative (5-HT-) cells isolated from the DRN. Our study revealed previously identified epigenetic loci, includingTNXBandPGLYRP1, and novel loci, includingRBMXL2,CAST,GNAT1,MALAT1, andDNAJB13. Strikingly, we found that the methylation profile ofTNXBdepends both on disease phenotype and cell type analyzed, emphasizing the significance of single cell(-type) neuroepigenetic studies in AD.
Publisher
Cold Spring Harbor Laboratory