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

NEUROBIOLOGY OF DISEASE

卷:36

Article

Shankar, Ganesh M.^1,2,3  Leissring, Malcolm A.^2,3  Adame, Anthony⁴  Sun, Xiaoyan^2,3  Spooner, Edward^2,3  Masliah, Eliezer⁴  Selkoe, Dennis J.^2,3  Lemere, Cynthia A.^2,3  Walsh, Dominic M.¹ 

[1] Univ Coll Dublin, Lab Neurodegenerat Res, Sch Biomol & Biomed Sci, Conway Inst Biomed & Biomol Res, Dublin 4, Ireland

[2] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[4] Univ Calif San Diego, Sch Med, Dept Neurosci, San Diego, CA 92093 USA

关键词: Amyloid beta-protein;    Aggregation;    Oligomers;    Amyloid precursor protein;    J20 mice;    Synaptophysin;    MAP2;   

DOI  :  10.1016/j.nbd.2009.07.021

来源: Elsevier

【 摘 要 】

The amyloid beta-protein (A beta) is believed to play a causal role in Alzheimer's disease, however, the mechanism by which A beta mediates its effect and the assembly form(s) of A beta responsible remain unclear. Several APP transgenic mice have been shown to accumulate A beta 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 A beta monomer and SDS-stable dimer. But prior to the earliest detection of A beta 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 A beta aggregates at the earliest ages studied. These data demonstrate the presence of multiple assembly forms of A beta throughout the life of J20 mice and highlight the difficulty in attributing synaptotoxicity to a single A beta species. (C) 2009 Elsevier Inc. All rights reserved.

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