Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential

Abstract

Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measure genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compare them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identify 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to “Parkinson’s disease” and “metabolic pathway”, as well as the diseases of “severe intellectual disability” and “mood disorders”. Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future.

Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: A DNA co-methylation network analysis

“…The copyright holder for this preprint (which this version posted July 23, 2023. ; https://doi.org/10.1101/2023.07. 20.549825 doi: bioRxiv preprint have shown robust alterations in DNA methylation in a number of genes in different neurodegenerative diseases, in both the brain and blood, including Alzheimer's disease (AD) [23][24][25] , PD [26][27][28] and Dementia with Lewy bodies (DLB) 29 . Interestingly, associations have also been reported for secondary symptoms of these neurodegenerative disease, for example with psychosis symptoms in AD 30 or cognition in PD 27 .…”

Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis

“…DNA methylation, which refers to the reversible addition of methyl groups to cytosines typically in a CpG dinucleotide, is the most studied epigenetic mechanism in neurological disorders 22 . Indeed, several studies have shown robust alterations in DNA methylation in a number of genes in different neurodegenerative diseases, in both the brain and blood, including Alzheimer's disease (AD) [23][24][25] , PD [26][27][28] and Dementia with Lewy bodies (DLB) 29 . Interestingly, associations have also been reported for secondary symptoms of these neurodegenerative disease, for example with psychosis symptoms in AD 30 or cognition in PD 27 .…”