Genetic factors such as the presence of the apolipoproteine e4 (APOE4) allele strongly increases an individual's risk for developing late-onset Alzheimer’s disease. Despite decades of research and thousands of studies, the pathogenic role of ApoE4 in Alzheimer’s disease has not been clearly elucidated. In order to clarify the role of APOE4 in the pathogenesis of Alzheimer’s disease, a systems biology approach was applied to transcriptomic and genomic data of APOE44 carriers affected by Alzheimer’s disease. Network analysis combined with a novel technique for biomarker computation allowed the identification of an alteration in ageing-associated processes such as inflammation, oxidative stress and metabolic pathways, indicating that APOE4 possibly accelerates pathological processes physiologically induced by ageing.
Integration of genomic data indicates that the Notch pathway could be the nodal molecular mechanism altered in APOE44 allele carries with Alzheimer’s disease. Interestingly, also PSEN1 and APP, genes mutated in the early onset AD, are closely linked to this pathway. Thus, in conclusion, ApoE4 role on inflammation and oxidation through the Notch signaling pathway could be crucial in elucidating the risk factors of AD.
Reference: Caberlotto L, Lauria M, Nguyen TP, Scotti M. The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis. PLoS One. 2013 Nov 12;8(11):e78919