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.

中文翻译：

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阿尔茨海默病中 Fc γ 受体介导的吞噬通路失调：基于网络的基因表达分析

转录组学已成为识别阿尔茨海默病 (AD) 中失调的生物途径的重要工具。我们使用 2 个独立的队列，阿尔茨海默病神经影像学倡议 (ADNI；N = 661) 和 AddNeuroMed (N = 674)，对基于血液的微阵列基因表达谱进行了基于网络的基因表达分析。加权基因共表达网络分析确定了来自 ADNI 的 17 个模块和来自 AddNeuroMed 的 13 个模块。ADNI衍生的四个模块与AD显着相关；AddNeuroMed 中的 5 个模块很重要。AD 相关模块的基因集富集分析确定并复制了 3 条生物途径，包括 Fc γ 受体介导的吞噬作用途径。基于模块的关联分析显示了 AD 相关模块，它具有 3 个途径，与认知功能和神经影像生物标志物相关联。基于基因的关联分析发现 Fc γ 受体介导的吞噬作用通路中的 PRKCD 与认知功能和脑脊液生物标志物显着相关。Fc γ 受体介导的吞噬作用途径的鉴定表明外周先天免疫系统与 AD 的病理生理学有关。已知 PRKCD 与淀粉样蛋白 β 诱导的神经变性有关。Fc γ 受体介导的吞噬作用途径的鉴定表明外周先天免疫系统与 AD 的病理生理学有关。已知 PRKCD 与淀粉样蛋白 β 诱导的神经变性有关。Fc γ 受体介导的吞噬作用途径的鉴定表明外周先天免疫系统与 AD 的病理生理学有关。已知 PRKCD 与淀粉样蛋白 β 诱导的神经变性有关。