title: Phosphoproteome analysis of an early onset mouse model (TgCRND8) of Alzheimer's disease reveals temporal changes in neuronal and glia signaling pathways.
abstract: 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.
authors: Key Lab of Separation Sciences for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, P. R. China.
authors: Fangjun
authors: F
authors: Wang
authors: Alexandre P
authors: AP
authors: Blanchard
authors: Fred
authors: F
authors: Elisma
authors: Matthew
authors: M
authors: Granger
authors: Hongbin
authors: H
authors: Xu
authors: Steffany A L
authors: SA
authors: Bennett
authors: Daniel
authors: D
authors: Figeys
authors: Hanfa
authors: H
authors: Zou
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007553:Isotope Labeling / Q000379:methods; D008569:Memory Disorders / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis* / Q000378:metabolism*; D010766:Phosphorylation; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D010750:Phosphoproteins