Park, Young HoHodges, AngelaRisacher, Shannon L.Lin, KuangJang, Jae-WonAhn, SoyeonKim, SangYunLovestone, SimonSimmons, AndrewWeiner, Michael W.Saykin, Andrew J.Nho, Kwangsik2022-09-192022-09-192020-04Park YH, Hodges A, Risacher SL, et al. Dysregulated Fc gamma receptor-mediated phagocytosis pathway in Alzheimer's disease: network-based gene expression analysis. Neurobiol Aging. 2020;88:24-32. doi:10.1016/j.neurobiolaging.2019.12.001https://hdl.handle.net/1805/30044Transcriptomics 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.en-USPublisher PolicyAlzheimer's diseaseCoexpressionPhagocytosisTranscriptomeArticle