Amyloid-β Alters the DNA Methylation Status of Cell-fate Genes in an Alzheimer's Disease Model

Taher, Noor; McKenzie, Courtney; Garrett, Rebecca; Baker, Matthew S; Fox, Nena; Isaacs, Gary D.

doi:10.3233/jad-131061

Cited by 26 publications

(17 citation statements)

References 47 publications

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“…In line, brain microvascular endothelial cells subjected to high levels of synthetic Aβ show lower levels of DNA methylation as measured by high-performance liquid chromatography (HPLC) ( Chen et al, 2009 ). Nevertheless, conversely to the previously discussed observations, IMR-32 neuroblastoma cells subjected to high levels of synthetic Aβ do not show significant alterations in DNA methylation as measured by DNA microarrays ( Taher et al, 2014 ).…”

Section: Epigenetic Alterations In Admentioning

confidence: 55%

Epigenetic Alterations in Alzheimer’s Disease

Sánchez-Mut

Gräff

2015

Front. Behav. Neurosci.

141

105

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Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

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Section: Epigenetic Alterations In Admentioning

confidence: 55%

Epigenetic Alterations in Alzheimer’s Disease

Sánchez-Mut

Gräff

2015

Front. Behav. Neurosci.

141

105

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“…These findings are linked to the recent observation that amyloid peptide treatments can induce DNA methylation alterations in genes involved in in vitro neuronal differentiation. 35 Other pathways associated with neurodegenerative diseases, such as altered cyclic nucleotide signaling, 36 illustrated by the protein kinase cAMP-dependent regulatory type I alpha ( PRKAR1A ) and the cGMP-dependent protein kinase type II ( PRKG2 ) genes, were also present in the identified DMRs. Interestingly, the characterized CpG methylation sites might also pinpoint newly recognized pathways in these disorders.…”

Section: Discussionmentioning

confidence: 99%

Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

et al. 2016

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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.

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“…The epigenetic mechanisms altered in AD may cause direct impairments to neurogenesis. As discussed above, DNA methylation, which is crucial for NSC proliferation, differentiation and migration, is disrupted in AD pathology, with resulting neurogenic impairment (8). In the SVZ of AD mice, increased histone H3 acetylation significantly reduces cell proliferation throughout life (9).…”

Section: Neurogenesis In Admentioning

confidence: 99%

Neurogenesis-based epigenetic therapeutics for Alzheimer's disease (Review)

Bao

Wang

2016

Molecular Medicine Reports

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Alzheimer's disease (AD) is a worldwide health problem with multiple pathogenic causes including aging, and genetic and environmental factors. As the interfaces between genes and the environment, epigenetic mechanisms, including DNA methylation, histone modification and microRNAs, are also involved in the pathogenesis of AD. Neurogenesis occurs throughout life in the normal adult brain of mammals. The neurogenic process, consisting of the proliferation, differentiation and maturation of neural stem cells (NSC), is regulated via epigenetic mechanisms by controlling the expression of specific sets of genes. In the pathology of AD, due to impairments in epigenetic mechanisms, the generation of neurons from NSCs is damaged, which exacerbates the loss of neurons and the deficits in learning and memory function associated with AD. Based on neurogenesis, a number of therapeutic strategies have shown capability in promoting neuronal generation to compensate for the neurons lost in AD, thereby improving cognitive function through epigenetic modifications. This provides potential for the treatment of AD by stimulating neurogenesis using epigenetic strategies. The present review discusses the epigenetics of AD and adult neurogenesis, and summarizes the neurogenesis-based epigenetic therapies targeted at AD. Such a review may offer information for the guidance of future developments of therapeutic strategies for AD.

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Amyloid-β Alters the DNA Methylation Status of Cell-fate Genes in an Alzheimer's Disease Model

Cited by 26 publications

References 47 publications

Epigenetic Alterations in Alzheimer’s Disease

Epigenetic Alterations in Alzheimer’s Disease

Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

Neurogenesis-based epigenetic therapeutics for Alzheimer's disease (Review)

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