- ELSEVIER IRELAND LTD
We previously identified the E693 Delta, mutation in amyloid precursor protein (APP) in patients with Alzheimer's disease (AD) and then generated APP-transgenic mice expressing this mutation. As these mice possessed abundant A beta oligomers from 8 months of age but no amyloid plaques even at 24 months of age, they are a good model to study pathological effects of amyloid beta (A beta) oligomers. The two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) technology, using a mixed-sample internal standard, is now recognized as an accurate method to determine and quantify proteins. In this study, we examined the proteins for which levels were altered in the hippocampus of 12-month-old APP(E693 Delta)-transgenic mice using 2D-DIGE and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fourteen proteins were significantly changed in the hippocampus of APP(E693 Delta)-transgenic mice. Actin cytoplasmic 1 (beta-actin), heat shock cognate 71 kDa, gamma-enolase, ATP synthase subunit beta, tubulin beta-2A chain, clathrin light chain B (clathrin) and dynamin-1 were increased. Heat shock-related 70 kDa protein 2, neurofilament light polypeptide (NFL), stress-induced-phosphoprotein 2, 60 kDa heat shock protein (HSP60), alpha-internexin, protein kinase C and casein kinase substrate in neurons protein 1 (Pacsin 1), alpha-enolase and beta-actin were decreased. Western blotting also validated the changed levels of HSP60, NFL, clathrin and Pacsin 1 in APP(E693 Delta)-transgenic mice. The identified proteins could be classified as cytoskeleton, chaperons, neurotransmission, energy supply and signal transduction. Thus, proteomics by 2D-DIGE and LC-MS/MS has provided knowledge of the levels of proteins in the early stages of AD brain. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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