Quantitative and Mechanistic Studies of A beta Immunotherapy

There is substantial and compelling evidence that aggregation and accumulation of amyloid beta protein (A beta) plays a pivotal role in the development of Alzheimer's disease (AD); thus, numerous strategies to prevent A beta aggregation and accumulation or to facilitate removal of preexisting deposits of A beta are being evaluated as ways to treat or prevent AD [1, 2]. Pre-clinical studies in mice demonstrate the therapeutic potential of altering A beta deposition by inducing a humoral immune response to fibrillar A beta 42 (fA beta 42) or passively administering anti-A beta antibodies (Abs) [3, 4], and both passive and active anti-A beta immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how A beta immunotherapy might work to attenuate or in some circumstances clear A beta from the brain, no mechanism has been definitively proven or disproven. Herein, we will review the various mechanisms that have been postulated. In addition we will discuss how a more thorough understanding of the pharmacokinetics of anti-A beta Abs and their effects on A beta levels and turnover provides insight into both the therapeutic potential and limitation of A beta immunotherapy. We will conclude with a discussion of additional experimentation-required to better understand the mechanism of action of anti-A beta Abs in AD and optimize antibody (Ab) mediated therapy for AD.