| Literature DB >> 29507413 |
Raffaella Nativio1, Greg Donahue1, Amit Berson2, Yemin Lan1, Alexandre Amlie-Wolf3, Ferit Tuzer4, Jon B Toledo3, Sager J Gosai2, Brian D Gregory2, Claudio Torres4, John Q Trojanowski3, Li-San Wang3, F Brad Johnson5, Nancy M Bonini6, Shelley L Berger7.
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.Entities:
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Year: 2018 PMID： 29507413 PMCID： PMC6124498 DOI： 10.1038/s41593-018-0101-9
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884