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

J Neurochem. 2005 Nov;95(3):834-47. doi: 10.1111/j.1471-4159.2005.03407.x. Epub 2005 Aug 31.


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.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Antibodies
  • Antibody Specificity
  • Cells, Cultured
  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes / metabolism
  • Fatty Acids
  • Hippocampus / cytology
  • Humans
  • Long-Term Potentiation
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism*
  • Neurons / pathology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Protein Conformation
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Water / metabolism


  • Amyloid beta-Peptides
  • Antibodies
  • Epitopes
  • Fatty Acids
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Water