Quantitative and mechanistic studies of Abeta immunotherapy.
There is substantial and compelling evidence that aggregation and accumulation of amyloid beta protein (Abeta) plays a pivotal role in the development of Alzheimer's disease (AD); thus, numerous strategies to prevent Abeta aggregation and accumulation or to facilitate removal of preexisting deposits of Abeta are being evaluated as ways to treat or prevent AD. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Abeta deposition by inducing a humoral immune response to fibrillar Abeta42 (fAbeta42) or passively administering anti-Abeta antibodies (Abs), and both passive and active anti-Abeta immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Abeta immunotherapy might work to attenuate or in some circumstances clear Abeta 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-Abeta Abs and their effects on Abeta levels and turnover provides insight into both the therapeutic potential and limitation of Abeta immunotherapy. We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Abeta Abs in AD and optimize antibody (Ab) mediated therapy for AD.
Golde
Todd E
TE
Mayo Clinic, College of Medicine, Department of Neuroscience, Mayo Clinic Florida, 4500 San Pablo Rd., Jacksonville, FL 32224, USA. tgolde@mayo.edu
Das
Pritam
P
Levites
Yona
Y
D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic
D016229:Amyloid beta-Peptides; D000906:Antibodies; D000939:Epitopes