Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease

B. Urbanc, L. Cruz, R. Le, J. Sanders, K. Hsiao Ashe, K. Duff, H. E. Stanley, M. C. Irizarry, B. T. Hyman

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

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 Aβ 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.

Original languageEnglish (US)
Pages (from-to)13990-13995
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number22
DOIs
StatePublished - Oct 29 2002

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