Grant: Project Grant

Alzheimer's disease is the most common form of dementia. We now understand that the first changes in the brain occur as early as 15-30 years before symptoms of Alzheimer's disease become evident. Therefore, new strategies are needed to both prevent and treat Alzheimer's disease. At the molecular level, protein fragments called amyloid-beta are produced in the brain and form the characteristic pathology that defines Alzheimer's disease. They thus constitute a specific marker of Alzheimer's disease. The goal of our research program is to identify molecular processes that have not been investigated before to stop Alzheimer's disease at early stages. Alzheimer's disease patients often suffer from hardening of blood vessels (atherosclerosis). Alzheimer's disease and atherosclerosis share the same risk factors, including high cholesterol levels in the blood, high blood pressure, and type II diabetes. There is a blood protein contributing to high levels of "bad" cholesterol called CETP. Blockers of CETP activity have been developed for the treatment of cardiovascular disease including atherosclerosis and myocardial infarct and have been tested in clinical trials. Interestingly, several genetic studies showed an association of CETP variants with maintenance of good brain functioning during aging. Some studies even implied that CETP variants may protect from Alzheimer's disease. However, CETP has never been investigated in relation to Alzheimer's disease on a molecular level. Results from our laboratory indicate that CETP has a strong impact on amyloid-beta formation. With the data generated in this project, we aim to able to initiate clinical trials to investigate if CETP blockers may be effective in preventing or treating Alzheimer's disease.