A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease

Nicholas T. Seyfried, Eric B. Dammer, Vivek Swarup, Divya Nandakumar, Duc M. Duong, Luming Yin, Qiudong Deng, Tram Nguyen, Chadwick M. Hales, Thomas Wingo, Jonathan Glass, Marla Gearing, Madhav Thambisetty, Juan C Troncoso, Daniel H. Geschwind, James J. Lah, Allan I. Levey

Research output: Contribution to journalArticle

Abstract

Here, we report proteomic analyses of 129 human cortical tissues to define changes associated with the asymptomatic and symptomatic stages of Alzheimer's disease (AD). Network analysis revealed 16 modules of co-expressed proteins, 10 of which correlated with AD phenotypes. A subset of modules overlapped with RNA co-expression networks, including those associated with neurons and astroglial cell types, showing altered expression in AD, even in the asymptomatic stages. Overlap of RNA and protein networks was otherwise modest, with many modules specific to the proteome, including those linked to microtubule function and inflammation. Proteomic modules were validated in an independent cohort, demonstrating some module expression changes unique to AD and several observed in other neurodegenerative diseases. AD genetic risk loci were concentrated in glial-related modules in the proteome and transcriptome, consistent with their causal role in AD. This multi-network analysis reveals protein- and disease-specific pathways involved in the etiology, initiation, and progression of AD.

Original languageEnglish (US)
Pages (from-to)60-72.e4
JournalCell Systems
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 25 2017

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Seyfried, N. T., Dammer, E. B., Swarup, V., Nandakumar, D., Duong, D. M., Yin, L., ... Levey, A. I. (2017). A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease. Cell Systems, 4(1), 60-72.e4. https://doi.org/10.1016/j.cels.2016.11.006