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Transcriptomics 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. Copyright © 2019 Elsevier Inc. All rights reserved.

Citation

Young Ho Park, Angela Hodges, Shannon L Risacher, Kuang Lin, Jae-Won Jang, Soyeon Ahn, SangYun Kim, Simon Lovestone, Andrew Simmons, Michael W Weiner, Andrew J Saykin, Kwangsik Nho, AddNeuroMed consortium and the Alzheimer's Disease Neuroimaging Initiative. Dysregulated Fc gamma receptor-mediated phagocytosis pathway in Alzheimer's disease: network-based gene expression analysis. Neurobiology of aging. 2020 Apr;88:24-32

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PMID: 31901293

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