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

Ganesh M. Shankar, Malcolm A. Leissring, Anthony Adame, Xiaoyan Sun, Edward Spooner, Eliezer Masliah, Dennis J. Selkoe, Cynthia A. Lemere, Dominic M. Walsh

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The amyloid β-protein (Aβ) is believed to play a causal role in Alzheimer's disease, however, the mechanism by which Aβ mediates its effect and the assembly form(s) of Aβ responsible remain unclear. Several APP transgenic mice have been shown to accumulate Aβ 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 Aβ monomer and SDS-stable dimer. But prior to the earliest detection of Aβ 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 Aβ aggregates at the earliest ages studied. These data demonstrate the presence of multiple assembly forms of Aβ throughout the life of J20 mice and highlight the difficulty in attributing synaptotoxicity to a single Aβ species.

Original languageEnglish (US)
Pages (from-to)293-302
Number of pages10
JournalNeurobiology of Disease
Volume36
Issue number2
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

Alzheimer Disease
Serum Amyloid A Protein
Synaptophysin
Immunoprecipitation
Transgenic Mice
Western Blotting
Enzyme-Linked Immunosorbent Assay
Staining and Labeling

Keywords

  • Aggregation
  • Amyloid β-protein
  • Amyloid precursor protein
  • J20 mice
  • MAP2
  • Oligomers
  • Synaptophysin

ASJC Scopus subject areas

  • Neurology

Cite this

Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Aβ assembly forms throughout life. / Shankar, Ganesh M.; Leissring, Malcolm A.; Adame, Anthony; Sun, Xiaoyan; Spooner, Edward; Masliah, Eliezer; Selkoe, Dennis J.; Lemere, Cynthia A.; Walsh, Dominic M.

In: Neurobiology of Disease, Vol. 36, No. 2, 11.2009, p. 293-302.

Research output: Contribution to journalArticle

Shankar, Ganesh M. ; Leissring, Malcolm A. ; Adame, Anthony ; Sun, Xiaoyan ; Spooner, Edward ; Masliah, Eliezer ; Selkoe, Dennis J. ; Lemere, Cynthia A. ; Walsh, Dominic M. / Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Aβ assembly forms throughout life. In: Neurobiology of Disease. 2009 ; Vol. 36, No. 2. pp. 293-302.
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