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

Malcolm A. Leissring¹  Anthony Adame²  Cynthia A. Lemere²  Edward Spooner²  Dominic M. Walsh²  Eliezer Masliah²  Xiaoyan Sun³  Dennis J. Selkoe³  Ganesh M. Shankar⁴ 

[1] Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA;Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA;Department of Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA 92093, USA;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;

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

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown