Drug development and PET-diagnostics for Alzheimer's disease.

ABSTRACT

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 beta. The alpha-, beta- and gamma-secretases are the three executioners of amyloid precursor protein processing. Significant progress has been made in the selective inhibition of these proteases, regardless of the availability of structural information. Several peptidic and non-peptidic leads were identified and first drug candidates are in clinical trials. Cholesterol lowering drugs and metal chelators are also in advanced clinical stages as disease modifiers. Successful trials demand either large cohorts or reliable markers for Alzheimer's disease. Therefore, several radiomarkers are under investigation to support such clinical trials.