title: Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity.
abstract: The accumulation of beta-amyloid (A beta) in neuritic plaques is thought to be causative for the progression of Alzheimer's disease (AD). Recently, both active immunization and passive administration of A beta 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-A beta 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-A beta antibodies) significantly lowered CSF levels of A beta in non-demented patients. In this study, anti-A beta antibodies were isolated from immunoglobulin preparations and these anti-A beta antibodies strongly block fibril formation or disrupt formation of fibrilar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of A beta. In contrast, immunoglobulins depleted of anti-A beta antibodies had little effect on A beta fibril formation or protection of neuronal cells. This study supports the findings that human anti-A beta antibodies may interfere with the pathogenesis of AD by more than one mechanism, and administration of polyclonal human anti-A beta antibodies isolated from plasma is a potential therapeutic agent to prevent or slow down disease progression.
authors.affiliation: Department of Neurology, School of Medicine, Indiana University,975 W. Walnut Street IB 457, Indianapolis, IN 46202, USA. ydu@iupui.edu
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
authors.forename: Norbert
authors.initials: N
authors.lastname: Sommer
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Ma
authors.forename: Liming
authors.initials: L
authors.lastname: Zhao
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Martin
authors.initials: M
authors.lastname: Farlow
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G