Under this guidance numerous AD drug candidates were developed that either deplete extracellular Aβ (e.g., various Aβ-specific monoclonal antibodies) or suppress the production of Aβ in the AβPP proteolytic pathway (e.g., inhibitors of the beta-site AβPP cleaving enzyme, BACE1, also known as beta-secretase). Here, BACE1 is linked to Alzheimer disease.