Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life.
Neurobiol Dis
; 36(2): 293-302, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19660551
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Modelos Animais de Doenças
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Doença de Alzheimer
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Longevidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2009
Tipo de documento:
Article