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Get Free AccessAbstract Recent 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 in TNXB was 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, including TNXB and PGLYRP1 , and novel loci, including RBMXL2 , CAST , GNAT1 , MALAT1 , and DNAJB13 . Strikingly, we found that the methylation profile of TNXB depends both on disease phenotype and cell type analyzed, emphasizing the significance of single cell(-type) neuroepigenetic studies in AD.
Renzo J. M. Riemens, Ehsan Pishva, Artemis Iatrou, Janou A. Y. Roubroeks, Jennifer Nolz, Roy Lardenoije, Mourad W. Ali, Antonio del Sol, Raúl Delgado‐Morales, Manel Esteller, Günter Kenis, BPF Rutten, Klaus‐Peter Lesch, Stephen D. Ginsberg, Paul D. Coleman, Jonathan Mill, Diego Mastroeni, Alfredo Ramı́rez, Thomas Haaf, Katie Lunnon, DLA van den Hove (2023). Epigenome-wide profiling in the dorsal raphe nucleus highlights cell-type-specific changes in<i>TNXB</i>in Alzheimer’s disease. , DOI: https://doi.org/10.1101/2023.08.28.555168.
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Type
Preprint
Year
2023
Authors
21
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1101/2023.08.28.555168
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