Integration of transcriptomic and genomic data suggests candidate mechanisms for APOE4-mediated pathogenic action in Alzheimer’s disease

Caberlotto, Laura, Marchetti, Luca, Lauria, Mario, Scotti, Marco and Parolo, Silvia (2016) Integration of transcriptomic and genomic data suggests candidate mechanisms for APOE4-mediated pathogenic action in Alzheimer’s disease Scientific Reports, 6 . p. 32583. DOI 10.1038/srep32583.

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Abstract

Among the genetic factors known to increase the risk of late onset Alzheimer's diseases (AD), the presence of the apolipoproteine e4 (APOE4) allele has been recognized as the one with the strongest effect. However, despite decades of research, the pathogenic role of APOE4 in Alzheimer's disease has not been clearly elucidated yet. In order to investigate the pathogenic action of APOE4, we applied a systems biology approach to the analysis of transcriptomic and genomic data of APOE44 vs. APOE33 allele carriers affected by Alzheimer's disease. Network analysis combined with a novel technique for biomarker computation allowed the identification of an alteration in aging-associated processes such as inflammation, oxidative stress and metabolic pathways, indicating that APOE4 possibly accelerates pathological processes physiologically induced by aging. Subsequent integration with genomic data indicates that the Notch pathway could be the nodal molecular mechanism altered in APOE44 allele carriers with Alzheimer's disease. Interestingly, PSEN1 and APP, genes whose mutation are known to be linked to early onset Alzheimer's disease, are closely linked to this pathway. In conclusion, APOE4 role on inflammation and oxidation through the Notch signaling pathway could be crucial in elucidating the risk factors of Alzheimer's disease.

Document Type: Article
Keywords: Diseases of the nervous system; Network models; Alzheimer
Research affiliation: OceanRep > GEOMAR > FB3 Marine Ecology > FB3-EOE-N Experimental Ecology - Food Webs
Refereed: Yes
DOI etc.: 10.1038/srep32583
ISSN: 2045-2322
Date Deposited: 23 Sep 2016 07:19
Last Modified: 03 May 2017 11:32
URI: http://eprints.uni-kiel.de/id/eprint/33999

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