Dysregulated Fc gamma receptor–mediated phagocytosis pathway in Alzheimer's disease: network-based gene expression analysis

AddNeuroMed consortium and the Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalNeurobiology of Aging
DOIs
StateAccepted/In press - Jan 1 2020

Fingerprint

Phagocytosis
Alzheimer Disease
Gene Expression
Neuroimaging
Cognition
Biomarkers
Gene Regulatory Networks
Transcriptome
Amyloid
Genes
Cerebrospinal Fluid
Immune System

Keywords

  • Alzheimer's disease
  • Coexpression
  • Network
  • Phagocytosis
  • PRKCD
  • Transcriptome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Dysregulated Fc gamma receptor–mediated phagocytosis pathway in Alzheimer's disease : network-based gene expression analysis. / AddNeuroMed consortium and the Alzheimer's Disease Neuroimaging Initiative.

In: Neurobiology of Aging, 01.01.2020.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Risacher, Shannon L.

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