Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology

J Biol Chem. 2006 Jan 20;281(3):1599-604. doi: 10.1074/jbc.M507892200. Epub 2005 Nov 10.


Accumulation of amyloid-beta (Abeta) is one of the earliest molecular events in Alzheimer disease (AD), whereas tau pathology is thought to be a later downstream event. It is now well established that Abeta exists as monomers, oligomers, and fibrils. To study the temporal profile of Abeta oligomer formation in vivo and to determine their interaction with tau pathology, we used the 3xTg-AD mice, which develop a progressive accumulation of plaques and tangles and cognitive impairments. We show that SDS-resistant Abeta oligomers accumulate in an age-dependent fashion, and we present evidence to show that oligomerization of Abeta appears to first occur intraneuronally. Finally, we show that a single intrahippocampal injection of a specific oligomeric antibody is sufficient to clear Abeta pathology, and more importantly, tau pathology. Therefore, Abeta oligomers may play a role in the induction of tau pathology, making the interference of Abeta oligomerization a valid therapeutic target.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Disease Models, Animal
  • Functional Laterality
  • Hippocampus / growth & development
  • Hippocampus / pathology
  • Humans
  • Macromolecular Substances / metabolism
  • Mice
  • Mice, Transgenic
  • Neurons / pathology
  • Recombinant Proteins / metabolism
  • tau Proteins / metabolism*


  • Amyloid beta-Peptides
  • Macromolecular Substances
  • Recombinant Proteins
  • tau Proteins