Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease
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Open Access
- 9 October 2002
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 99 (22) , 13990-13995
- https://doi.org/10.1073/pnas.222433299
Abstract
Despite extensive deposition of putatively neurotoxic amyloid-β (Aβ) protein in the brain, it has not been possible to demonstrate an association of Aβ deposits with neuronal loss in Alzheimer's disease (AD), and neuronal loss is minimal in transgenic mouse models of AD. Using triple immunostaining confocal microscopy and analyzing the images with the cross-correlation density map method from statistical physics, we directly compared Aβ deposition, Aβ morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar Aβ deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Aβ develops neurotoxic properties in vivo when it adopts a fibrillar β-pleated sheet conformation.Keywords
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