The exact cause of Alzheimer ’ s disease is still unknown; despite the dramatic progress in understanding. Most gene mutations associated with Alzheimer's disease point to the amyloid precursor protein and amyloid β. The α-, β- and γ-secretases execute the amyloid precursor protein processing. Significant progress has been made in the selective inhibition and modulation of these proteases, regardless of the availability of structural information. Peptidic and nonpeptidic leads were identified and several drug candidates are 2008 in clinical trials. Successful trials demand either large cohorts or reliable biological surrogate markers for Alzheimer's disease. Therefore, several radio markers are under investigation to support such clinical trials by PET-imaging. Here we summarize the developments until 2006 and highlight the important developments until 2008.
Keywords: Alzheimer's disease, secretase, copper, aspartic protease, cholesterol, imaging
