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

doi:10.1073/pnas.222433299

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

Journal article

Open access

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 and B T Hyman

Proceedings of the National Academy of Sciences - PNAS, v 99(22), pp 13990-13995

29 Oct 2002

DOI: https://doi.org/10.1073/pnas.222433299

PMID: 12374847

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Abstract

Thiazoles - metabolism

Presenilin-1

Membrane Proteins - genetics

Humans

Male

Mice, Transgenic

Alzheimer Disease - pathology

Plaque, Amyloid

Animals

Alzheimer Disease - metabolism

Amyloid beta-Peptides - metabolism

Female

Neurotoxins - metabolism

Mice

Disease Models, Animal

Despite extensive deposition of putatively neurotoxic amyloid-beta (Abeta) protein in the brain, it has not been possible to demonstrate an association of Abeta 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 Abeta deposition, Abeta morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar Abeta deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Abeta develops neurotoxic properties in vivo when it adopts a fibrillar beta-pleated sheet conformation.

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189 citations in Web of Science

203 citations in Scopus

Details

Title: Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease
Creators: B Urbanc - Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215, USA. brigita@bu.edu
L Cruz
R Le
J Sanders
K Hsiao Ashe
K Duff
H E Stanley
M C Irizarry
B T Hyman
Publication Details: Proceedings of the National Academy of Sciences - PNAS, v 99(22), pp 13990-13995
Publisher: PNAS; United States
Grant note: P41 RR013622 / NCRR NIH HHS AG15453 / NIA NIH HHS AG15379 / NIA NIH HHS AG08487 / NIA NIH HHS R01 AG008487 / NIA NIH HHS AG00793 / NIA NIH HHS P41 RR13622 / NCRR NIH HHS P01 AG015379 / NIA NIH HHS P01 AG017216 / NIA NIH HHS AG17216 / NIA NIH HHS P01 AG015453 / NIA NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: Physics
Web of Science ID: WOS:000178967400007
Scopus ID: 2-s2.0-0037195163
Other Identifier: 991014877787704721

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Collaboration types: Domestic collaboration
Web of Science research areas: Neurosciences

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

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Abstract

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UN Sustainable Development Goals (SDGs)

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