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

The accumulation of beta-amyloid (Abeta) in neuritic plaques is thought to be causative for the progression of Alzheimer's disease (AD). Recently, both active immunization and passive administration of Abeta 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-Abeta 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-Abeta antibodies) significantly lowered CSF levels of Abeta in non-demented patients. In this study, anti-Abeta antibodies were isolated from immunoglobulin preparations and these anti-Abeta antibodies strongly block fibril formation or disrupt formation of fibrilar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of Abeta. In contrast, immunoglobulins depleted of anti-Abeta antibodies had little effect on Abeta fibril formation or protection of neuronal cells. This study supports the findings that human anti-Abeta antibodies may interfere with the pathogenesis of AD by more than one mechanism, and administration of polyclonal human anti-Abeta antibodies isolated from plasma is a potential therapeutic agent to prevent or slow down disease progression.