Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer’s disease
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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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Thioflavin S-positive fibrillary Aβ deposits contribute to focal neuronal toxicity, at least in their immediate environment, as shown in AD cases and AD transgenic mice.
“Nonetheless, thioflavin S-positive fibrillary Aβ deposits contribute to focal neuronal toxicity, at least in their immediate environment, as shown in both AD cases and AD transgenic mice [36]”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [36]
β-sheet-structured Aβ may be neurotoxic.
“𝛃 -Sheet-structured A 𝛃 may be neurotoxic (Urbanc et al., 2002)”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Urbanc et al., 2002
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“Nonetheless, thioflavin S-positive fibrillary Aβ deposits contribute to focal neuronal toxicity, at least in their immediate environment, as shown in both AD cases and AD transgenic mice [36] and local oxidative stress surrounding plaques has been proposed as a potential mechanism contributing to selective neuronal de…”
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Self-citation
- 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
- Publisher
- National Academy of Sciences
- Published
- 2002-10-09
- Volume
- 99
- Issue
- 22
- Pages
- 13990-13995
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC137824
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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