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Cell Syst. 2017 Jan 25;4(1):60-72.e4. doi: 10.1016/j.cels.2016.11.006. Epub 2016 Dec 15.

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

Author information

1
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: nseyfri@emory.edu.
2
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
3
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
4
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
5
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA; Division of Neurology, Atlanta VA Medical Center, Decatur, GA 30033, USA.
6
Department of Experimental Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
7
Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
8
Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
9
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: alevey@emory.edu.

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.

Comment in

PMID:
27989508
PMCID:
PMC5269514
DOI:
10.1016/j.cels.2016.11.006
[Indexed for MEDLINE]
Free PMC Article

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