Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity.
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.
Du
Yansheng
Y
Department of Neurology, School of Medicine, Indiana University,975 W. Walnut Street IB 457, Indianapolis, IN 46202, USA. ydu@iupui.edu
Wei
Xing
X
Dodel
Richard
R
Sommer
Norbert
N
Hampel
Harald
H
Gao
Feng
F
Ma
Zhizhong
Z
Zhao
Liming
L
Oertel
Wolfgang H
WH
Farlow
Martin
M
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
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G