Epitopes described in "Globular amyloid beta-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease."

Article Authors:Stefan Barghorn; Volker Nimmrich; Andreas Striebinger; Carsten Krantz; Patrick Keller; Bodo Janson; Michael Bahr; Martin Schmidt; Robert S Bitner; John Harlan; Eve Barlow; Ulrich Ebert; Heinz Hillen
Article Title:Globular amyloid beta-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease.
Reference Detail
Reference ID:1010142
Abstract:Amyloid beta-peptide (Abeta)(1-42) oligomers have recently been discussed as intermediate toxic species in Alzheimer's disease (AD) pathology. Here we describe a new and highly stable Abeta(1-42) oligomer species which can easily be prepared in vitro and is present in the brains of patients with AD and Abeta(1-42)-overproducing transgenic mice. Physicochemical characterization reveals a pure, highly water-soluble globular 60-kDa oligomer which we named 'Abeta(1-42) globulomer'. Our data indicate that Abeta(1-42) globulomer is a persistent structural entity formed independently of the fibrillar aggregation pathway. It is a potent antigen in mice and rabbits eliciting generation of Abeta(1-42) globulomer-specific antibodies that do not cross-react with amyloid precursor protein, Abeta(1-40) and Abeta(1-42) monomers and Abeta fibrils. Abeta(1-42) globulomer binds specifically to dendritic processes of neurons but not glia in hippocampal cell cultures and completely blocks long-term potentiation in rat hippocampal slices. Our data suggest that Abeta(1-42) globulomer represents a basic pathogenic structural principle also present to a minor extent in previously described oligomer preparations and that its formation is an early pathological event in AD. Selective neutralization of the Abeta globulomer structure epitope is expected to have a high potential for treatment of AD.
Reference Type:Literature
PubMed ID:16135089
Journal:J Neurochem
Journal Volume:95
Article Pages:834-47
Journal ISSN:1471-4159
Article Chemical List:Amyloid beta-Peptides;Antibodies;Epitopes;Fatty Acids;Peptide Fragments;amyloid beta-protein (1-42);Water
Article MeSH List:Alzheimer Disease(metabolism; pathology; physiopathology); Amyloid beta-Peptides(chemistry; genetics; immunology; metabolism); Animals; Antibodies; Antibody Specificity; Cells, Cultured; Epitopes(chemistry; immunology; metabolism); Fatty Acids; Hippocampus(cytology); Humans; Long-Term Potentiation; Male; Mice; Mice, Transgenic; Neurons(metabolism; pathology); Peptide Fragments(chemistry; genetics; immunology; metabolism); Protein Conformation; Rabbits; Rats; Rats, Sprague-Dawley; Solubility; Water(metabolism)
Curation Last Updated:2014-10-03 21:05:50