Human anti-β-amyloid antibodies block β-amyloid fibril formation and prevent β-amyloid-induced neurotoxicity

Yansheng Du, Xing Wei, Richard Dodel, Norbert Sommer, Harald Hampel, Feng Gao, Zhizhong Ma, Liming Zhao, Wolfgang H. Oertel, Martin Farlow

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

The accumulation of β-amyloid (Aβ) in neuritic plaques is thought to be causative for the progression of Alzheimer's disease (AD). Recently, both active immunization and passive administration of Aβ antibodies dramatically attenuated amyloid plaque deposition, neuritic dystrophy, astrogliosis and behaviour deficits in transgenic animals. In addition, we and others have found that titres of naturally occurring anti-Aβ antibodies in the CSF of AD patients are significantly lower than those in age-matched controls. Treatment with intravenous immunoglobulins (a preparation that contained anti-Aβ antibodies) significantly lowered CSF levels of Aβ in non-demented patients. In this study, anti-Aβ antibodies were isolated from immunoglobulin preparations and these anti-Aβ antibodies strongly block fibril formation or disrupt formation of fibrillar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of Aβ. In contrast, immunoglobulins depleted of anti-Aβ antibodies had little effect on Aβ fibril formation or protection of neuronal cells. This study supports the findings that human anti-Aβ antibodies may interfere with the pathogenesis of AD by more than one mechanism, and administration of polyclonal human anti-Aβ antibodies isolated from plasma is a potential therapeutic agent to prevent or slow down disease progression.

Original languageEnglish (US)
Pages (from-to)1935-1939
Number of pages5
JournalBrain
Volume126
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • β-amyloid
  • Aβ antibodies
  • Alzheimer's disease
  • Immunotherapy
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)

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    Du, Y., Wei, X., Dodel, R., Sommer, N., Hampel, H., Gao, F., Ma, Z., Zhao, L., Oertel, W. H., & Farlow, M. (2003). Human anti-β-amyloid antibodies block β-amyloid fibril formation and prevent β-amyloid-induced neurotoxicity. Brain, 126(9), 1935-1939. https://doi.org/10.1093/brain/awg191