Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life

Neurobiol Dis. 2009 Nov;36(2):293-302. doi: 10.1016/j.nbd.2009.07.021. Epub 2009 Aug 4.


The amyloid beta-protein (Abeta) is believed to play a causal role in Alzheimer's disease, however, the mechanism by which Abeta mediates its effect and the assembly form(s) of Abeta responsible remain unclear. Several APP transgenic mice have been shown to accumulate Abeta and to develop cognitive deficits. We have studied one such model, the J20 mouse. Using an immunoprecipitation/Western blotting technique we find an age-dependent increase in Abeta monomer and SDS-stable dimer. But prior to the earliest detection of Abeta dimers, immunohistochemical analysis revealed an increase in oligomer immunoreactivity that was coincident with reduced hippocampal MAP2 and synaptophysin staining. Moreover, biochemical fractionation and ELISA analysis revealed evidence of TBS and triton-insoluble sedimentable Abeta aggregates at the earliest ages studied. These data demonstrate the presence of multiple assembly forms of Abeta throughout the life of J20 mice and highlight the difficulty in attributing synaptotoxicity to a single Abeta species.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Disease Models, Animal*
  • Humans
  • Immunoprecipitation
  • Longevity / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Isoforms / toxicity
  • Synapses / drug effects
  • Synapses / physiology


  • Amyloid beta-Peptides
  • Protein Isoforms