SWATH analysis of the synaptic proteome in Alzheimer's disease

Chang, Rachel Yoon Kyung, Etheridge, Naomi, Nouwens, Amanda S. and Dodd, Peter R. (2015) SWATH analysis of the synaptic proteome in Alzheimer's disease. Neurochemistry International, 87 1-12. doi:10.1016/j.neuint.2015.04.004


Author Chang, Rachel Yoon Kyung
Etheridge, Naomi
Nouwens, Amanda S.
Dodd, Peter R.
Title SWATH analysis of the synaptic proteome in Alzheimer's disease
Journal name Neurochemistry International   Check publisher's open access policy
ISSN 0197-0186
1872-9754
Publication date 2015-08
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.neuint.2015.04.004
Open Access Status Not yet assessed
Volume 87
Start page 1
End page 12
Total pages 12
Place of publication London, United Kingdom
Publisher Elsevier
Collection year 2016
Language eng
Abstract Brain tissue from Alzheimer's disease patients exhibits synaptic degeneration in selected regions. Synaptic dysfunction occurs early in the disease and is a primary pathological target for treatment. The molecular mechanisms underlying this degeneration remain unknown. Quantifying the synaptic proteome in autopsy brain and comparing tissue from Alzheimer's disease cases and subjects with normal aging are critical to understanding the molecular mechanisms associated with Alzheimer pathology. We isolated synaptosomes from hippocampus and motor cortex so as to reduce sample complexity relative to whole-tissue homogenates. Synaptosomal extracts were subjected to strong cation exchange (SCX) fractionation to further partition sample complexity; each fraction received SWATH-based information-dependent acquisition to generate a comprehensive peptide-ion library. The expression of synaptic proteins from AD hippocampus and motor cortex was then compared between groups. A total of 2077 unique proteins were identified at a critical local false discovery rate <5%. Thirty of these, including 17 novel proteins, exhibited significant expression differences between cases and controls; these proteins are involved in cellular functions including structural maintenance, signal transduction, autophagy, oxidative stress, and proteasome activity, or they have synaptic-vesicle related or energy-related functions. Differentially expressed proteins were subjected to pathway analysis to identify protein-protein interactions. This revealed that the most perturbed molecular and cellular functions were cellular assembly and organization. Core analysis revealed RhoA signaling to be the top canonical pathway. Network analysis showed that differentially expressed proteins were related to cellular assembly and organization, and cellular function and maintenance. This is the first study to combine SCX fractionation with SWATH analysis. SWATH is a promising new technique that can greatly enhance protein identification in any proteome, and has many other benefits; however, there are limitations yet to be resolved.
Keyword Human
Proteomics
HPLC
Cerebral cortex
Pathway analysis
Cellular assembly and organization
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 19 Jun 2015, 12:50:23 EST by Anthony Yeates on behalf of School of Chemistry & Molecular Biosciences