Proteomics Analysis Of Brain Tissue Of B6C3-Tg(APPswe,PSEN1dE9)mice

Alzheimer’s disease (AD) is the most common cause of dementia. Mice in the transgenic APPswe/PS1dE9mouse line express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and mutant human presenilin1(PS1-dE9) associated with early-onset Alzheimer’s disease. Knowing the protein expression in these mice may offer better understanding of the pathological changes in AD. In this study, we used two-dimensional gel electrophoresis combined with mass spectrometry techniques to compare protein expression in APPswe/PS1dE9mice with age-matched wild-type mice throughout the disease progression. We identified12proteins that were significantly different between the APPswe/PS1dE9mice and age-matched controls and also changed with disease development. Among those, the expression levels of the following proteins in APPswe/PS1dE9mice were at least1.5times higher than those in normal mice:pyruvate dehydrogenase El component subunit beta mitochondrial, serum albumin, creatine kinase B-type, heat shock70kDa protein1A and Adenylate kinase isoenzyme1. Levels of the following proteins in APPswe/PS1dE9mice were at least1.5times lower than those in normal mice: dihydropyrimidinase-related protein2, actin cytoplasmic1, actin cytoplasmic2, F-actin-capping protein, V-type proton ATPase catalytic subunit A, tubulin alphas-1C chain, subunit alpha-2and ubiquitin carboxyl-terminal hydrolase isozyme L1. These proteins are involved in regulating various cellular functions, including cytoskeletal structure, energy metabolism, synaptic components, and protein degradation. These findings indicate altered protein expression in the pathogenesis of AD and illuminate novel therapeutic avenues for treatment in AD.