Proteomic 2-D DIGE profiling of APP23 transgenic mice brain from pre-plaque and plaque phenotypes.
Alzheimer's disease is the most prevalent form of dementia associated with aging in the human population for which there is no biomarker for accurate and effective diagnosis at its early stage or monitoring of disease progression. In this study, we used 2-D DIGE to identify Alzheimer's disease-related proteins in the brains of APP23 mice used as a model for studying cerebral amyloidosis. Protein expression profiles in the brain of 2- and 24-month old female transgenic mice, displaying pre-plaque and plaque phenotypes, respectively, and 24-month old wild-type mice were compared to identify if changes at the protein level could be implicated in the early molecular events leading to cerebral amyloidosis. Seven such proteins were identified including kinesin heavy chain, dihydropyrimidinase related protein 2, beta-tubulin, two isomers of 3-phosphoglycerate dehydrogenase, ubiquinol cytochrome c reductase, and heat shock protein 84. The dysregulation of these proteins may have implications on pathways such as the mitochondrial respiratory chain, axonal transport, axon guidance, L-Serine biosynthesis and cytoskeletal reorganization, and thereby may represent events that precede and participate in the formation of senile plaque. Other detected protein changes were observed only in the plaque phenotype, and so are likely to be a consequence of plaque deposition and/or associated with neurodegenerative/repair processes. These proteins provide a basis for further dissecting the early mechanisms of Alzheimer's disease, and exploring their implications as relevant biomarker candidates of incipient Alzheimer's disease and progression in man.
Guerreiro
Nelson
N
BioMarker Development, Novartis, Klybeckstrasse, Basel, Switzerland. nelson.guerreiro@novartis.com
Staufenbiel
Matthias
M
Gomez-Mancilla
Baltazar
B
D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D030561:Databases, Nucleic Acid; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D058225:Plaque, Amyloid / Q000378:metabolism*; D040901:Proteomics / Q000295:instrumentation*
D016564:Amyloid beta-Protein Precursor