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학술저널
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대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제50권
발행연도
2018.1
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1 - 15 (15page)

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Aging is an inevitable progressive decline in every physiological function and serves as a primary risk factor for cognitive decline and Alzheimer’s disease. Thus, age-dependent impairments in cognitive function must be understood in association with general aging processes with an integrative approach in a systemic manner. An integrative aging gene network was constructed based on mutual molecular interactions using literature-curated interactome data and separated into functionally distinct modules. To investigate key surrogate biomarkers of the aging brain in the context of the general aging process, co-expression networks were built on post-mortem and Alzheimer’s brain transcriptome data. In both the normal aging brain and the brain affected by Alzheimer’s disease, the immune-related co-expression module was positively correlated with advancing age, whereas the synaptic transmission-related co-expression module was decreased with age. Importantly, the network topology-based analysis indicated that complement system genes were prioritized as a surrogate biomarker in evaluating the process of brain aging. Our public data-centered analysis coupled with experimental validation revealed that the complement system is likely to be a master regulator in initiating and regulating the immune system in the aging brain and could serve as reliable and surrogate biomarkers for the diagnosis of cognitive dysfunction.

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