TY - JOUR
T1 - Quantitative and mechanistic studies of Aβ immunotherapy
AU - Golde, Todd E.
AU - Das, Pritam
AU - Levites, Yona
PY - 2009
Y1 - 2009
N2 - There is substantial and compelling evidence that aggregation and accumulation of amyloid β protein (Aβ) plays a pivotal role in the development of Alzheimer's disease (AD); thus, numerous strategies to prevent Aβ aggregation and accumulation or to facilitate removal of preexisting deposits of Aβ are being evaluated as ways to treat or prevent AD [1,2]. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Aβ deposition by inducing a humoral immune response to fibrillar Aβ42 (fAβ42) or passively administering anti-Aβ antibodies (Abs) [3, 4], and both passive and active anti-Aβ immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Aβ immunotherapy might work to attenuate or in some circumstances clear Aβ 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-Aβ Abs and their effects on Aβ levels and turnover provides insight into both the therapeutic potential and limitation of Aβ immunotherapy. We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Aβ Abs in AD and optimize antibody (Ab) mediated therapy for AD.
AB - There is substantial and compelling evidence that aggregation and accumulation of amyloid β protein (Aβ) plays a pivotal role in the development of Alzheimer's disease (AD); thus, numerous strategies to prevent Aβ aggregation and accumulation or to facilitate removal of preexisting deposits of Aβ are being evaluated as ways to treat or prevent AD [1,2]. Pre-clinical studies in mice demonstrate the therapeutic potential of altering Aβ deposition by inducing a humoral immune response to fibrillar Aβ42 (fAβ42) or passively administering anti-Aβ antibodies (Abs) [3, 4], and both passive and active anti-Aβ immunotherapeutic approaches are now being tested in humans. Although a variety of mechanisms have been postulated regarding how Aβ immunotherapy might work to attenuate or in some circumstances clear Aβ 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-Aβ Abs and their effects on Aβ levels and turnover provides insight into both the therapeutic potential and limitation of Aβ immunotherapy. We will conclude with a discussion of additional experimentation required to better understand the mechanism of action of anti-Aβ Abs in AD and optimize antibody (Ab) mediated therapy for AD.
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U2 - 10.2174/187152709787601830
DO - 10.2174/187152709787601830
M3 - Review article
C2 - 19275635
AN - SCOPUS:65649091306
SN - 1871-5273
VL - 8
SP - 31
EP - 49
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
IS - 1
ER -