ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Amyloid β peptide (Aβ) is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the form of Aβ that induces neurodegeneration in AD, defined here as bioactive Aβ, is not clear. Preventing the formation of bioactive Aβ or inactivating previously formed bioactive Aβ should be a promising approach to treat AD. We have previously developed a cell-based assay for the detection of bioactive Aβ species. The assay is based upon the correlation between the ability of an Aβ sample to induce a unique form of cellular MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] formazan exocytosis, and its ability to activate glia and induce neurotoxicity. Here, we show that this cell-based assay is not only useful for a cellular model of Aβ amyloidogenesis but is also able to detect bioactive Aβ species in a transgenic mouse model of AD, as well as in post-mortem cortex samples from AD patients. There is a good correlation between the extent of glia activation and the level of bioactive Aβ species in the mouse brain. A promising deuteroporphyrin that can inactivate bioactive Aβ species was also identified using this assay. These novel insights and findings should have important implications for the treatment of AD.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.2004.02751.x
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