DNA methylation patterns in the frontal lobe white matter of multiple system atrophy, Parkinson's disease, and progressive supranuclear palsy: A cross-comparative investigation DOI Creative Commons
Megha Murthy, Katherine Fodder, Yasuo Miki

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 11, 2024

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by neuronal loss and gliosis, with oligodendroglial cytoplasmic inclusions (GCI's) containing alpha-synuclein being the primary pathological hallmark. Clinical presentations of MSA overlap other parkinsonian disorders such as Parkinson's (PD), dementia Lewy bodies (DLB), progressive supranuclear palsy (PSP), posing challenges in early diagnosis. Numerous studies have reported perturbations DNA methylation diseases, candidate loci identified various including MSA, PD, PSP. Although PSP present substantial white matter pathology, alterations also been PD. However, comparing architectures these diseases are lacking. We therefore aimed to investigate three PSP, identify shared disease-specific matter. Genome-wide profiling frontal lobe individuals (n=17), PD (n=16) controls (n=15), using Illumina EPIC array, revealed commonalities further used weighted gene correlation network analysis disease-associated co-methylation signatures dysregulation processes relating Wnt signalling, signal transduction, endoplasmic reticulum stress, mitochondrial processes, RNA interference, endosomal transport. Our results highlight several pathways indicative converging molecular mechanisms contributing towards neurodegeneration all diseases.

Language: Английский

DNA methylation patterns in the frontal lobe white matter of multiple system atrophy, Parkinson's disease, and progressive supranuclear palsy: A cross-comparative investigation DOI Creative Commons
Megha Murthy, Katherine Fodder, Yasuo Miki

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 11, 2024

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by neuronal loss and gliosis, with oligodendroglial cytoplasmic inclusions (GCI's) containing alpha-synuclein being the primary pathological hallmark. Clinical presentations of MSA overlap other parkinsonian disorders such as Parkinson's (PD), dementia Lewy bodies (DLB), progressive supranuclear palsy (PSP), posing challenges in early diagnosis. Numerous studies have reported perturbations DNA methylation diseases, candidate loci identified various including MSA, PD, PSP. Although PSP present substantial white matter pathology, alterations also been PD. However, comparing architectures these diseases are lacking. We therefore aimed to investigate three PSP, identify shared disease-specific matter. Genome-wide profiling frontal lobe individuals (n=17), PD (n=16) controls (n=15), using Illumina EPIC array, revealed commonalities further used weighted gene correlation network analysis disease-associated co-methylation signatures dysregulation processes relating Wnt signalling, signal transduction, endoplasmic reticulum stress, mitochondrial processes, RNA interference, endosomal transport. Our results highlight several pathways indicative converging molecular mechanisms contributing towards neurodegeneration all diseases.

Language: Английский

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