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Integrative genomics identifies APOE ε4 effectors in Alzheimer's disease.
- Source :
-
Nature . 8/1/2013, Vol. 500 Issue 7460, p45-50. 6p. 1 Diagram, 4 Graphs. - Publication Year :
- 2013
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 500
- Issue :
- 7460
- Database :
- Academic Search Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 89496489
- Full Text :
- https://doi.org/10.1038/nature12415