Insights from proteomics into mild cognitive impairment, likely the earliest stage of Alzheimer's disease

Mild cognitive impairment (MCI) is arguably the earliest form of Alzheimer's disease (AD). Better understanding of brain changes in MCI may lead to the identification of therapeutic targets to slow the progression of AD. Oxidative stress has been implicated as a mechanism associated with the pathogenesis of both MCI and AD. In particular, among other markers, there is evidence for an increase in the levels of protein oxidation and lipid peroxidation in the brains of subjects with MCI. Several proteins are oxidatively modified in MCI brain, and as a result individual protein dysfunction may be directly linked to these modifications (e.g., carbonylation, nitration, modification by HNE) and may be involved in MCI pathogenesis. Additionally, Concanavalin-A-mediated separation of brain proteins has recently led to the identification of key proteins in MCI and AD using proteomics methods. This chapter will summarize important findings from proteomics studies of MCI, which have provided insights into this cognitive disorder and have led to further understanding of potential mechanisms involved in the progression of AD.