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Dysregulation of the epigenetic landscape of normal aging in Alzheimer’s disease
- Source :
- Nature Neuroscience. 21:497-505
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Aging is the strongest risk factor for Alzheimer’s disease (AD), although the underlying mechanisms remain unclear. The chromatin state, in particular through the mark H4K16ac, has been implicated in aging and thus may play a pivotal role in age-associated neurodegeneration. Here we compare the genome-wide enrichment of H4K16ac in the lateral temporal lobe of AD individuals against both younger and elderly cognitively normal controls. We found that while normal aging leads to H4K16ac enrichment, AD entails dramatic losses of H4K16ac in the proximity of genes linked to aging and AD. Our analysis highlights the presence of three classes of AD-related changes with distinctive functional roles. Furthermore, we discovered an association between the genomic locations of significant H4K16ac changes with genetic variants identified in prior AD genome-wide association studies and with expression quantitative trait loci. Our results establish the basis for an epigenetic link between aging and AD.
- Subjects :
- Epigenomics
Male
0301 basic medicine
Aging
Chromatin Immunoprecipitation
Histone Deacetylase 1
Disease
Biology
Article
Epigenesis, Genetic
Temporal lobe
03 medical and health sciences
Alzheimer Disease
medicine
Humans
Epigenetics
Aged
Genetic association
Analysis of Variance
General Neuroscience
Neurodegeneration
Brain
Middle Aged
medicine.disease
Chromatin
030104 developmental biology
Expression quantitative trait loci
Female
Neuroscience
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15461726 and 10976256
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Nature Neuroscience
- Accession number :
- edsair.doi.dedup.....339124c304f57be19a3aae365dbca80b