TY  - JOUR
A1  - Kim, Jae Ho
A1  - Franck, Julien
A1  - Kang, Taewook
A1  - Heinsen, Helmut
A1  - Ravid, Rivka
A1  - Ferrer, Isidro
A1  - Cheon, Mi Hee
A1  - Lee, Joo-Yong
A1  - Yoo, Jong Shin
A1  - Steinbusch, Harry W.
A1  - Salzet, Michel
A1  - Fournier, Isabelle
A1  - Park, Young Mok
T1  - Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer's disease
JF  - Scientific Reports
N2  - 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.
KW  - imaging mass spectrometry
KW  - neuron navigator 3
KW  - dentate gyrus
KW  - growth factor
KW  - mouse model
KW  - neurotrophic factor
KW  - entorhinal cortex
KW  - factor expression
KW  - oxidative stress
KW  - memory deficits
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151727
VL  - 5
IS  - 11138
ER  -