BACKGROUND: The loss of synaptic function is a pivotal mechanism in the development of Alzheimer's Disease (AD). Structural changes and loss of plasticity in the postsynaptic density (PSD) may contribute to the pathogenesis. However, the underlying molecular events triggering synaptic dysfunction remain elusive. We report a quantitative proteomic analysis of the PSD from human postmortem brain tissues of possible and definite AD cases. METHODS: The analysis used both discovery and targeted mass spectrometry approaches and was repeated with biological replicates. During the discovery study, we compared several hundred proteins in the PSD-enriched fractions and found that 25 proteins were differentially regulated in AD. RESULTS: Interestingly, the majority of these protein changes were larger in definite AD cases than in possible AD cases. In the targeted analysis, we measured the level of 9 core PSD proteins and found that only IRSp53 was highly down-regulated in AD. The alteration of selected proteins (i.e. internexin and IRSp53) was further validated by immunoblotting against 7 control and 8 AD cases. CONCLUSIONS: These results expand our understanding of how AD impacts PSD composition, and hints at new hypotheses for AD pathogenesis.
BACKGROUND: The loss of synaptic function is a pivotal mechanism in the development of Alzheimer's Disease (AD). Structural changes and loss of plasticity in the postsynaptic density (PSD) may contribute to the pathogenesis. However, the underlying molecular events triggering synaptic dysfunction remain elusive. We report a quantitative proteomic analysis of the PSD from human postmortem brain tissues of possible and definite AD cases. METHODS: The analysis used both discovery and targeted mass spectrometry approaches and was repeated with biological replicates. During the discovery study, we compared several hundred proteins in the PSD-enriched fractions and found that 25 proteins were differentially regulated in AD. RESULTS: Interestingly, the majority of these protein changes were larger in definite AD cases than in possible AD cases. In the targeted analysis, we measured the level of 9 core PSD proteins and found that only IRSp53 was highly down-regulated in AD. The alteration of selected proteins (i.e. internexin and IRSp53) was further validated by immunoblotting against 7 control and 8 AD cases. CONCLUSIONS: These results expand our understanding of how AD impacts PSD composition, and hints at new hypotheses for AD pathogenesis.
Authors: Junmin Peng; Myung Jong Kim; Dongmei Cheng; Duc M Duong; Steven P Gygi; Morgan Sheng Journal: J Biol Chem Date: 2004-03-12 Impact factor: 5.157
Authors: Mark O Collins; Holger Husi; Lu Yu; Julia M Brandon; Chris N G Anderson; Walter P Blackstock; Jyoti S Choudhary; Seth G N Grant Journal: J Neurochem Date: 2006-04 Impact factor: 5.372
Authors: Junmin Peng; Joshua E Elias; Carson C Thoreen; Larry J Licklider; Steven P Gygi Journal: J Proteome Res Date: 2003 Jan-Feb Impact factor: 4.466
Authors: R D Terry; E Masliah; D P Salmon; N Butters; R DeTeresa; R Hill; L A Hansen; R Katzman Journal: Ann Neurol Date: 1991-10 Impact factor: 10.422
Authors: Tracey C Dickson; Jyoti A Chuckowree; Meng Inn Chuah; Adrian K West; James C Vickers Journal: Neurobiol Dis Date: 2005-03 Impact factor: 5.996
Authors: Domenico Taverna; Alonda C Pollins; Lillian B Nanney; Giovanni Sindona; Richard M Caprioli Journal: Exp Dermatol Date: 2015-11-23 Impact factor: 3.960
Authors: Bing Bai; Ping-Chung Chen; Chadwick M Hales; Zhiping Wu; Vishwajeeth Pagala; Anthony A High; Allan I Levey; James J Lah; Junmin Peng Journal: J Proteome Res Date: 2014-06-13 Impact factor: 4.466
Authors: Àlex Bayés; Mark O Collins; Clare M Galtrey; Clémence Simonnet; Marcia Roy; Mike D R Croning; Gemma Gou; Louie N van de Lagemaat; David Milward; Ian R Whittle; Colin Smith; Jyoti S Choudhary; Seth G N Grant Journal: Mol Brain Date: 2014-11-28 Impact factor: 4.041