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Browsing by Author "Ahn, Soyeon"
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Item Dysregulated Fc gamma receptor-mediated phagocytosis pathway in Alzheimer’s disease: network-based gene expression analysis(Elsevier, 2020-04) Park, Young Ho; Hodges, Angela; Risacher, Shannon L.; Lin, Kuang; Jang, Jae-Won; Ahn, Soyeon; Kim, SangYun; Lovestone, Simon; Simmons, Andrew; Weiner, Michael W.; Saykin, Andrew J.; Nho, Kwangsik; Radiology and Imaging Sciences, School of MedicineTranscriptomics has become an important tool for identification of biological pathways dysregulated in Alzheimer's disease (AD). We performed a network-based gene expression analysis of blood-based microarray gene expression profiles using 2 independent cohorts, Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 661) and AddNeuroMed (N = 674). Weighted gene coexpression network analysis identified 17 modules from ADNI and 13 from AddNeuroMed. Four of the modules derived in ADNI were significantly related to AD; 5 modules in AddNeuroMed were significant. Gene-set enrichment analysis of the AD-related modules identified and replicated 3 biological pathways including the Fc gamma receptor-mediated phagocytosis pathway. Module-based association analysis showed the AD-related module, which has the 3 pathways, to be associated with cognitive function and neuroimaging biomarkers. Gene-based association analysis identified PRKCD in the Fc gamma receptor-mediated phagocytosis pathway as being significantly associated with cognitive function and cerebrospinal fluid biomarkers. The identification of the Fc gamma receptor-mediated phagocytosis pathway implicates the peripheral innate immune system in the pathophysiology of AD. PRKCD is known to be related to neurodegeneration induced by amyloid-β.