Proteomics of Alzheimer's Disease mouse models

Alzheimer’s disease (AD) is a neurodegenerative disease displaying plaques formed by the neurotoxic amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relates to the massive neuronal death that occurs in AD brains remain elusive. To identify proteins, the levels of which are affected by increased Aβ levels, we performed a proteomic analysis of the AD mouse model APPsw and compared it to that of APPsw mice lacking the major Aβ degrading enzyme neprilysin. This was achieved by establishing an LC-MS/MS method to analyze brain homogenate, using an 18O-labeled internal standard to accurately quantify the protein levels. By this approach we identified approximately 600 proteins and could quantify the levels of 300 of these. Interestingly, several proteins, including some not previously reported to be associated with AD, were identified. The relevance of these proteins for AD warrants further research.