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However, despite decades of research, the pathogenic role of APOE4 in Alzheimer\u2019s 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\u2009vs. APOE33 allele carriers affected by Alzheimer\u2019s 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\u2019s disease. Interestingly, PSEN1 and APP, genes whose mutation are known to be linked to early onset Alzheimer\u2019s 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\u2019s disease.<\/jats:p>","DOI":"10.1038\/srep32583","type":"journal-article","created":{"date-parts":[[2016,9,2]],"date-time":"2016-09-02T09:06:53Z","timestamp":1472807213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Integration of transcriptomic and genomic data suggests candidate mechanisms for APOE4-mediated pathogenic action in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"6","author":[{"given":"Laura","family":"Caberlotto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Lauria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Parolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,2]]},"reference":[{"key":"BFsrep32583_CR1","unstructured":"Corey-Bloom, J. 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