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Beta-amyloid treatment of two complementary P301L tau-expressing Alzheimer's disease models reveals similar deregulated cellular processes.
- Source :
-
Proteomics [Proteomics] 2006 Dec; Vol. 6 (24), pp. 6566-77. - Publication Year :
- 2006
-
Abstract
- Alzheimer's disease (AD) is characterized by Abeta peptide-containing plaques and tau-containing neurofibrillary tangles (NFTs). Both pathologies have been combined by crossing Abeta plaque-forming APP mutant mice with NFT-forming P301L tau mutant mice or by stereotaxically injecting beta-amyloid peptide 1-42 (Abeta42) into brains of P301L tau mutant mice. In cell culture, Abeta42 induces filamentous tau aggregates. To understand which processes are disrupted by Abeta42 in the presence of tau aggregates, we applied comparative proteomics to Abeta42-treated P301L tau-expressing neuroblastoma cells and the amygdala of P301L tau transgenic mice stereotaxically injected with Abeta42. 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 Abeta42 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 Abeta42-mediated pathogenic cascade in AD and further support the role of unfolded proteins in the course of AD.
- Subjects :
- Alzheimer Disease etiology
Animals
Brain metabolism
Cell Line, Tumor
Disease Models, Animal
Humans
Mice
Mice, Transgenic
Mutation
Nerve Tissue Proteins isolation & purification
Nerve Tissue Proteins metabolism
Protein Folding
Proteomics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Alzheimer Disease genetics
Alzheimer Disease metabolism
Amyloid beta-Peptides pharmacology
tau Proteins genetics
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1615-9853
- Volume :
- 6
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proteomics
- Publication Type :
- Academic Journal
- Accession number :
- 17111439
- Full Text :
- https://doi.org/10.1002/pmic.200600634