Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life.
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.
Shankar
Ganesh M
GM
Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Sciences, Conway Institute for Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland.
Leissring
Malcolm A
MA
Adame
Anthony
A
Sun
Xiaoyan
X
Spooner
Edward
E
Masliah
Eliezer
E
Selkoe
Dennis J
DJ
Lemere
Cynthia A
CA
Walsh
Dominic M
DM
D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D047468:Immunoprecipitation; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D016229:Amyloid beta-Peptides; D020033:Protein Isoforms