Abstract
There is substantial and compelling evidence that aggregation and accumulation of amyloid β protein (Aβ) plays a pivotal role in the development of Alzheimers 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.
Keywords: Aβ Immunotherapy, Alzheimer's disease (AD), β protein, vaccination, Aβ amyloid
CNS & Neurological Disorders - Drug Targets
Title: Quantitative and Mechanistic Studies of Aβ Immunotherapy
Volume: 8 Issue: 1
Author(s): Todd E. Golde, Pritam Das and Yona Levites
Affiliation:
Keywords: Aβ Immunotherapy, Alzheimer's disease (AD), β protein, vaccination, Aβ amyloid
Abstract: There is substantial and compelling evidence that aggregation and accumulation of amyloid β protein (Aβ) plays a pivotal role in the development of Alzheimers 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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Cite this article as:
Golde E. Todd, Das Pritam and Levites Yona, Quantitative and Mechanistic Studies of Aβ Immunotherapy, CNS & Neurological Disorders - Drug Targets 2009; 8 (1) . https://dx.doi.org/10.2174/187152709787601830
DOI https://dx.doi.org/10.2174/187152709787601830 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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