Integrative genomics identifies APOE ε4 effectors in Alzheimer's disease

Herve Rhinn, Ryousuke Fujita, Liang Qiang, Rong Cheng, Joseph H. Lee and Asa Abeliovich ()
Additional contact information
Herve Rhinn: Cell Biology, and Neurology, Columbia University, 650 W. 168th Street, New York, New York 10032, USA
Ryousuke Fujita: Cell Biology, and Neurology, Columbia University, 650 W. 168th Street, New York, New York 10032, USA
Liang Qiang: Cell Biology, and Neurology, Columbia University, 650 W. 168th Street, New York, New York 10032, USA
Rong Cheng: Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, 650 W. 168th Street, New York, New York 10032, USA
Joseph H. Lee: Taub Institute for Alzheimer's Disease and the Aging Brain, Columbia University, 650 W. 168th Street, New York, New York 10032, USA
Asa Abeliovich: Cell Biology, and Neurology, Columbia University, 650 W. 168th Street, New York, New York 10032, USA

Nature, 2013, vol. 500, issue 7460, 45-50

Abstract: Abstract Late-onset Alzheimer’s disease (LOAD) risk is strongly influenced by genetic factors such as the presence of the apolipoprotein E ε4 allele (referred to here as APOE4), as well as non-genetic determinants including ageing. To pursue mechanisms by which these affect human brain physiology and modify LOAD risk, we initially analysed whole-transcriptome cerebral cortex gene expression data in unaffected APOE4 carriers and LOAD patients. APOE4 carrier status was associated with a consistent transcriptomic shift that broadly resembled the LOAD profile. Differential co-expression correlation network analysis of the APOE4 and LOAD transcriptomic changes identified a set of candidate core regulatory mediators. Several of these—including APBA2, FYN, RNF219 and SV2A—encode known or novel modulators of LOAD associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. Furthermore, a genetic variant within RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. These data implicate an APOE4 associated molecular pathway that promotes LOAD.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature12415 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:500:y:2013:i:7460:d:10.1038_nature12415

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature12415

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().