These authors contributed equally to this work.
Phosphoproteome analysis of an early onset mouse model (TgCRND8) of Alzheimer's disease reveals temporal changes in neuronal and glia signaling pathways
Article first published online: 2 APR 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Special Issue: FOCUS ON INTEGRATIVE PROTEOMICS
Volume 13, Issue 8, pages 1292–1305, April 2013
How to Cite
Wang, F., Blanchard, A. P., Elisma, F., Granger, M., Xu, H., Bennett, S. A. L., Figeys, D. and Zou, H. (2013), Phosphoproteome analysis of an early onset mouse model (TgCRND8) of Alzheimer's disease reveals temporal changes in neuronal and glia signaling pathways. Proteomics, 13: 1292–1305. doi: 10.1002/pmic.201200415
Colour Online: See the article online to view Figs. , and in colour.
- Issue published online: 12 APR 2013
- Article first published online: 2 APR 2013
- Accepted manuscript online: 18 JAN 2013 04:06AM EST
- Manuscript Accepted: 8 NOV 2012
- Manuscript Revised: 19 OCT 2012
- Manuscript Received: 8 SEP 2012
- NSFC. Grant Numbers: 21021004, 81161120540
- CIHR. Grant Numbers: CCI-117960, TGF-96121
- Alzheimer's disease;
- Animal model;
- Animal proteomics;
Sustained exposure to soluble amyloid β (Aβ42) oligomers is predicted to impair synaptic function in the hippocampal-entorhinal circuit, signaling synaptic loss and precipitating cognitive impairment in Alzheimer's disease. Regional changes in overall patterns of protein phosphorylation are likely crucial to promote transition from a presymptomatic to a symptomatic state in response to accumulating Aβ42. Here, we used unbiased proteomic approaches to compare the phosphoproteome of presymptomatic and symptomatic TgCRND8 mice and identify network disruptions in signaling pathways implicated in the manifestation of behavioral indices of learning and memory impairment. Phosphopeptide enrichment with triple isotopic dimethylation labeling combined with online multidimensional separation and MS was used to profile phosphoproteome changes in 2- and 6-month-old TgCRND8 mice and congenic littermate controls. We identified 1026 phosphopeptides representing 1168 phosphorylation sites from 476 unique proteins. Of these, 595 phosphopeptides from 293 unique proteins were reliably quantified and 139 phosphopeptides were found to change significantly in the hippocampus of TgCRND8 mice following conversion from a presymptomatic to a symptomatic state.