Using Proteomics to Understand Alzheimer’s Disease Pathogenesis

Our current understanding of the molecular changes that drive Alzheimer's disease (AD) pathogenesis is incomplete. Unbiased, mass spectrometry-based proteomic studies provide an efficient and comprehensive way to quantitatively examine thousands of proteins at once using microscopic amounts of human brain tissue. Recently, the number of proteomic studies that examine protein changes in AD brain tissue has been increasing. This chapter reviews the different proteomic approaches currently being used to identify pathological protein changes in AD brain tissue including bulk tissue studies that examine protein changes throughout the progression of AD, studies of the insoluble proteome in AD, studies using proteomics to examine selective vulnerability in AD, studies of the amyloid plaque and neurofibrillary tangle proteome, studies of the synaptic proteome, and studies of the interactome of beta amyloid and tau. Combined, these complementary proteomic approaches provide increased understanding about the protein changes that occur in the AD brain. Results from these proteomic studies provide an excellent resource for future hypothesis-driven targeted studies and will help identify new biomarkers of disease and new drug targets for AD.