Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers....

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Published in:Scientific reports 2015-06, Vol.5 (1), p.11138-11138, Article 11138
Main Authors: Ho Kim, Jae, Franck, Julien, Kang, Taewook, Heinsen, Helmut, Ravid, Rivka, Ferrer, Isidro, Hee Cheon, Mi, Lee, Joo-Yong, Shin Yoo, Jong, Steinbusch, Harry W, Salzet, Michel, Fournier, Isabelle, Mok Park, Young
Format: Article
Language:English
Subjects:
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Alzheimer Disease - metabolism
Alzheimer's disease
Bioinformatics
Biomarkers
Biomarkers - metabolism
Brain-derived neurotrophic factor
Cyclosporin A
Dementia disorders
Dentate gyrus
Dentate Gyrus - metabolism
Hippocampus
Humanities and Social Sciences
Humans
Immunoblotting
Insulin-like growth factor I
Life Sciences
Mass spectrometry
Mass spectroscopy
multidisciplinary
Myc protein
Neurodegenerative diseases
Proteins
Proteome
Science
Signal Transduction
Upstream
ZAP-70 protein
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Summary:Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep11138