| Autor: |
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 |
| Rok vydání: |
2005 |
| Předmět: |
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| Zdroj: |
Journal of neurochemistry. 95(3) |
| ISSN: |
0022-3042 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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