Brain Advance Access originally published online on June 23, 2003
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Brain, Vol. 126, No. 9, 1935-1939,
September 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg191
Human anti-ß-amyloid antibodies block ß-amyloid fibril formation and prevent ß-amyloid-induced neurotoxicity
1 Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, 2 Department of Neurology, Friedrich-Wilhelms-University, Bonn, 3 Department of Neurology, Philipps University, Marburg and 4 Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany
Correspondence to: Yansheng Du, PhD, Department of Neurology, School of Medicine, Indiana University,975 W. Walnut Street IB 457, Indianapolis, IN 46202, USA E-mail: ydu{at}iupui.edu
The accumulation of ß-amyloid (Aß) in neuritic plaques is thought to be causative for the progression of Alzheimer’s disease (AD). Recently, both active immunization and passive administration of Aß 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-Aß 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-Aß antibodies) significantly lowered CSF levels of Aß in non-demented patients. In this study, anti-Aß antibodies were isolated from immunoglobulin preparations and these anti-Aß antibodies strongly block fibril formation or disrupt formation of fibrilar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of Aß. In contrast, immunoglobulins depleted of anti-Aß antibodies had little effect on Aß fibril formation or protection of neuronal cells. This study supports the findings that human anti-Aß antibodies may interfere with the pathogenesis of AD by more than one mechanism, and administration of polyclonal human anti-Aß antibodies isolated from plasma is a potential therapeutic agent to prevent or slow down disease progression.
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