Quantitative and mechanistic studies of Aβ immunotherapy

Todd E. Golde, Pritam Das, Yona Levites

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-49
Number of pages19
JournalCNS and Neurological Disorders - Drug Targets
Volume8
Issue number1
DOIs
StatePublished - 2009

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Immunotherapy
Anti-Idiotypic Antibodies
Alzheimer Disease
Serum Amyloid A Protein
Humoral Immunity
Therapeutics
Pharmacokinetics
Antibodies
Brain
Clinical Studies
Alzheimer disease type 2
Alzheimer disease type 1

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)
  • Pharmacology

Cite this

Quantitative and mechanistic studies of Aβ immunotherapy. / Golde, Todd E.; Das, Pritam; Levites, Yona.

In: CNS and Neurological Disorders - Drug Targets, Vol. 8, No. 1, 2009, p. 31-49.

Research output: Contribution to journalArticle

Golde, Todd E. ; Das, Pritam ; Levites, Yona. / Quantitative and mechanistic studies of Aβ immunotherapy. In: CNS and Neurological Disorders - Drug Targets. 2009 ; Vol. 8, No. 1. pp. 31-49.
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