PXD014376

PXD014376 is an original dataset announced via ProteomeXchange.

Title	Membrane-Enriched Brain Proteome Across Stages of Alzheimer's Disease
Description	Previous systems-based proteomic approaches have characterized alterations in protein co-expression networks of unfractionated asymptomatic (AsymAD) and symptomatic Alzheimer’s disease (AD) brains. However, it remains unclear how sample fractionation and sub-proteomic analysis influences the organization of these protein networks and their relationship to clinicopathological traits of disease. In this proof-of-concept study, we performed a systems-based sub-proteomic analysis of membrane-enriched post-mortem brain samples from pathology-free control, AsymAD, and AD brains (n=6 per group). Label-free mass spectrometry based on peptide ion intensity was used to quantify the 18 membrane-enriched fractions. Differential expression and weighted protein co-expression network analysis (WPCNA) were then used to identify and characterize modules of co-expressed proteins most significantly altered between the groups. We identified a total of 27 modules of co-expressed membrane-associated proteins. In contrast to the unfractionated proteome, these networks did not map strongly to cell-type specific markers. Instead, these modules were principally organized by their associations with a wide variety of membrane-bound compartments and organelles. Of these, the mitochondrion was associated with the greatest number of modules, followed by modules linked to the cell surface compartment. In addition, we resolved networks with strong associations to the endoplasmic reticulum, Golgi apparatus, nucleus, and other membrane-bound organelles. Fourteen of the 27 modules demonstrated significant correlations with clinical and pathological AD phenotypes. These results revealed that the proteins within individual compartments feature a heterogeneous array of AD-associated expression patterns, particularly during preclinical stages of disease. In conclusion, this systems-based analysis of the membrane-associated AsymAD brain proteome yielded a unique network organization highly linked to cellular compartmentalization. Further study of this membrane-associated proteome may reveal novel insight into the complex pathways governing the earliest stages of disease.
HostingRepository	PRIDE
AnnounceDate	2019-09-02
AnnouncementXML	Submission_2019-09-02_06:24:21.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Dammer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-25 02:40:11	ID requested
⏵ 1	2019-09-02 06:24:22	announced

Higginbotham L, Dammer EB, Duong DM, Modeste E, Montine TJ, Lah JJ, Levey AI, Seyfried NT, Network Analysis of a Membrane-Enriched Brain Proteome across Stages of Alzheimer's Disease. Proteomes, 7(3):(2019) [pubmed]

submitter keyword: AD, transmembrane proteins, synaptic proteome

Nicholas T. Seyfried
contact affiliation	Emory University School of Medicine Department of Biochemistry
contact email	nseyfri@emory.edu
lab head
Eric Dammer
contact affiliation	Emory University
contact email	edammer@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014376
     1. Label: PRIDE project
     2. Name: Membrane-Enriched Brain Proteome Across Stages of Alzheimer's Disease