Format

Send to

Choose Destination
Nat Neurosci. 2018 Apr;21(4):497-505. doi: 10.1038/s41593-018-0101-9. Epub 2018 Mar 5.

Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease.

Author information

1
Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
3
Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
4
Department of Pathology, Drexel University College of Medicine, Philadelphia, PA, USA.
5
Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. johnsonb@pennmedicine.upenn.edu.
6
Department of Biology, University of Pennsylvania, Philadelphia, PA, USA. nbonini@sas.upenn.edu.
7
Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. bergers@pennmedicine.upenn.edu.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center