Treatment Strategies Targeting Amyloid β-Protein

With the advent of the key discovery in the mid-1980s that the amyloid beta-protein (A beta) is the core constituent of the amyloid plaque pathology found in Alzheimer disease (AD), an intensive effort has been underway to attempt to mitigate its role in the hope of treating the disease. This effort fully matured when it was clarified that the A beta is a normal product of cleavage of the amyloid precursor protein, and well-defined proteases for this process were identified. Further therapeutic options have been developed around the concept of anti-A beta aggregation inhibitors and the surprising finding that immunization with A beta itself leads to reduction of pathology in animal models of the disease. Here we review the progress in this field toward the goal of targeting A beta for treatment and prevention of AD and identify some of the major challenges for the future of this area of medicine.