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Journal article
Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease
Nature neuroscience, v 21(4), pp 497-505
Apr 2018
PMID: 29507413
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease
- Creators
- Raffaella Nativio - University of PennsylvaniaGreg Donahue - University of PennsylvaniaAmit Berson - University of PennsylvaniaYemin Lan - University of PennsylvaniaAlexandre Amlie-Wolf - University of PennsylvaniaFerit Tuzer - Drexel UniversityJon B Toledo - University of PennsylvaniaSager J Gosai - University of PennsylvaniaBrian D Gregory - University of PennsylvaniaClaudio Torres - Drexel UniversityJohn Q Trojanowski - University of PennsylvaniaLi-San Wang - University of PennsylvaniaF Brad Johnson - University of PennsylvaniaNancy M Bonini - University of PennsylvaniaShelley L Berger - University of Pennsylvania
- Publication Details
- Nature neuroscience, v 21(4), pp 497-505
- Publisher
- Springer Nature
- Grant note
- P30 ES013508 / NIEHS NIH HHS R35 NS097275 / NINDS NIH HHS R01 NS078283 / NINDS NIH HHS P01 AG017586 / NIA NIH HHS P30 AG010124 / NIA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000428796000009
- Scopus ID
- 2-s2.0-85042872962
- Other Identifier
- 991019168182204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences