Cited by 237Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Urbanc, B., Cruz, L., Le, R., Sanders, J., Ashe, K. Hsiao, Duff, K., Stanley, H. E., Irizarry, M. C. +1 more·2002·Proceedings of the National Academy of Sciences

Abstract

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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Authors
Urbanc, B., Cruz, L., Le, R., Sanders, J., Ashe, K. H., Duff, K., Stanley, H. E., Irizarry, M. C., & Hyman, B. T.
Affiliations
  • Boston University (US)
  • Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215; Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02219; Department of Neurology, University of Minnesota, Minneapolis, MN 55455; and Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962
Venue
Proceedings of the National Academy of Sciences
Published
2002-10-09
Volume
99
Issue
22
Pages
13990-13995
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2146188406
Cited by
237
References
41
Citations by year
2026: 4 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 13 · 2014: 17 · 2013: 9 · 2012: 12
FWCI
7.81
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health (AG08487, AG 15379, AG00793, AG17216)
  • National Institute on Aging (P01AG015379, AG-08487, AG 15453, R01AG008487, P01AG015453, AG15379, AG 17216, P01AG017216, AG00793)
  • National Center for Research Resources (P41RR013622, P41 RR13622)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, Alzheimer's disease, thioflavin S, neurotoxicity, neuronal loss, computer simulation
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Female, Humans, Male, Membrane Proteins, Mice, Transgenic, Neurotoxins, Thiazoles, Amyloid beta-Peptides, Mice, Benzothiazoles, Presenilin-1, Plaque, Amyloid

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