Alzheimer's disease (AD) is an age-related neurodegenerative disorder and the most common form of dementia. It is clinically characterized by a progressive impairment of cognitive functions (i.e.memory, reasoning) ultimately disrupting daily life activities. Unfortunately, there is still no effective test available to predict the development of AD nor are there effective therapies. This can be partially attributed to the limited knowledge that we have regarding the factors promoting/contributing to the development of AD. Noteworthy, the tissue protein composition of a person differs between physiological and pathological conditions (i.e.non-demented vs AD). Part of the protein changes observed in a pathological condition likely contribute to the development of the disease and thus, the identification of such changes in the earliest stages of disease evolution through proteomics approaches can unravel novel markers and insights in the cause of the disorder. In this project, we want to identify those protein changes that are critical for the development of AD. To do so, we will compare the levels of more than 1300 proteins in the brain tissue of specific non-demented patients to the levels in tissue of patients in early AD stages. We will analyze those proteins in a specific brain area, the hippocampus, which is involved in learning and memory and is one of the first to become strongly affected. It will be done using a novel and sensitive technique called SOMAscan. Unlike other proteomics approaches, with this technology we will later be able to use the reagents that detected the specific protein changes to further investigate the most interesting proteins. Those investigations will allow us not only to effectively validate the results but, more importantly, to target the mechanisms by which the identified proteins are involved in AD, which will open new insights and possibilities in the development of novel alternative therapeutic strategies.