β-amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes

David, Della C., Ittner, Lars M., Gehrig, Peter, Nergenau, Denise, Shepherd, Claire, Halliday, Glenda and Gotz, Juergen (2006) β-amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes. Proteomics, 6 24: 6566-6577. doi:10.1002/pmic.200600634


Author David, Della C.
Ittner, Lars M.
Gehrig, Peter
Nergenau, Denise
Shepherd, Claire
Halliday, Glenda
Gotz, Juergen
Title β-amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes
Journal name Proteomics   Check publisher's open access policy
ISSN 1615-9853
1615-9861
Publication date 2006-12-01
Year available 2006
Sub-type Article (original research)
DOI 10.1002/pmic.200600634
Open Access Status Not yet assessed
Volume 6
Issue 24
Start page 6566
End page 6577
Total pages 12
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Language eng
Formatted abstract
Alzheimer's disease (AD) is characterized by Aβ peptide-containing plaques and tau-containing neurofibrillary tangles (NFTs). Both pathologies have been combined by crossing Aβ plaque-forming APP mutant mice with NFT-forming P301L tau mutant mice or by stereotaxically injecting β-amyloid peptide 1-42 (Aβ42) into brains of P301L tau mutant mice. In cell culture, Aβ42 induces filamentous tau aggregates. To understand which processes are disrupted by Aβ42 in the presence of tau aggregates, we applied comparative proteomics to Aβ42- treated P301L tau-expressing neuroblastoma cells and the amygdala of P301L tau transgenic mice stereotaxically injected with Aβ42. Remarkably, a significant fraction of proteins altered in both systems belonged to the same functional categories, i.e. stress response and metabolism. We also identified model-specific effects of Aβ42 treatment such as differences in cell signaling proteins in the cellular model and of cytoskeletal and synapse associated proteins in the amygdala. By Western blotting (WB) and immunohistochemistry (IHC), we were able to show that 72% of the tested candidates were altered in human AD brain with a major emphasis on stress-related unfolded protein responsive candidates. These data highlight these processes as potentially important initiators in the Aβ42- mediated pathogenic cascade in AD and further support the role of unfolded proteins in the course of AD.
Keyword Alzheimer
Comparative proteomics
Neuroblastoma
Transgenic
Two-dimensional gel electrophoresis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
 
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