Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

Abstract

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.

Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks

“…However, there have been a handful of studies on other data modalities such as shared protein dysregulation (Hosp et al 2015) and shared epigenomic patterns (Urdinguio et al 2009; Portela and Esteller 2010; Sanchez-Mut et al 2016). These additional data modalities can provide unique information that is not captured at the transcriptome level and, when more comprehensively investigated in the future, can be integrated into system-wide network models to better capture the shared aetiology between neurodegenerative diseases.…”

Details matter: the role of genomic location and assay standardization in DNA methylation analyses

“…This is not surprising, considering the essential role DNA methylation plays in regulating gene expression [2], impacting essential processes such as cell differentiation. Inactivation of the DNA methyltransferases causes embryonic lethality in mice [3,4], underscoring the importance of correct DNA methylation patterns during normal development, with implications not only in health, but also disease.Aberrant DNA methylation has been reported in, for example, cardiovascular [5], neurodegenerative [6] and metabolic [7] disease. A link between DNA methylation and cancer was demonstrated as early as 1983, when a substantial proportion of CpG sites that were methylated in normal tissues were found to be unmethylated in cancer cells [8].…”

“…Aberrant DNA methylation has been reported in, for example, cardiovascular [5], neurodegenerative [6] and metabolic [7] disease. A link between DNA methylation and cancer was demonstrated as early as 1983, when a substantial proportion of CpG sites that were methylated in normal tissues were found to be unmethylated in cancer cells [8].…”

Nanomedicine and epigenome. Possible health risks

“…AD, dementia with Lewy bodies, PD and AD-like neurodegenerative profile associated with Down's syndrome. This finding is particularly important, suggesting that neurodegenerative disorders might have similar early pathogenic mechanisms that subsequently evolve into clinical entities with different molecular and cellular features (Sanchez-Mut et al, 2016). Although the aetiology of sporadic AD is still uncertain, environmental factors such as diet and exposure to heavy metals were shown to be involved, specifically in its late-onset form.…”