Proteomics Analysis in Alzheimer's Disease: New Insights into Mechanisms of Neurodegeneration

Publisher Summary Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder associated with cognitive decline and aging. A number of proteins are oxidatively modified in AD brain.The expression of many proteins is altered in the AD brain, resulting in a cascade of potential alterations of multiple pathways within the brain. The relationship between these pathways maintains a balance between neuronal survival and neuronal death. The coupling of two-dimensional gel electrophoresis and improvement of mass spectrometry (MS) techniques has allowed for the rapid screening and identification of proteins. The tools that have made proteomics possible as well as their application to AD are discussed. The tools for proteomics are: (1) 2D polyacrylamide gel electrophoresis; (2) nontraditional proteomics [2D-high-performance liquid chromatography (HPLC), isotope-coded affinity tags, protein phosphorylation, and membrane proteins]; (3) mass spectrometry (MALDI, ESI LC-MS and SELDI-TOF); and (4) database searching are outlined in the chapter. The expression alterations observed in many proteins involved in a number of pathways help to develop testable hypotheses of neurodegenerative mechanisms in AD brain. The application of proteomics to transgenic models of AD is an increasing field of research in AD. Such approaches allow the methods of testing the effects of genetic mutations associated with AD on specific proteins at both the expression and post-translational modification levels. Additionally, transgenic knock-in and knock-out mice allow for the study of the effect of inactivation of specific proteins that have been found to be oxidized in AD brain.