Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.

Lorenzo, A; Yankner, B A

doi:10.1073/pnas.91.25.12243

Cited by 1,324Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.

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Lorenzo, A, Yankner, B A·1994·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.91.25.12243PMC PMC45413

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Abstract

beta-Amyloid (beta A) is normally produced as a nontoxic soluble peptide. In Alzheimer disease, beta A aggregates and accumulates in the brain as inert diffuse plaques or compact plaques associated with neurodegenerative changes. To determine the relationship of neurotoxicity to the physical state of beta A, we created (i) nonamyloidogenic amorphous aggregates of beta A [amorphous beta A (Am-beta A)] analogous to diffuse plaques and (ii) amyloidogenic fibrils of beta A [fibrillar beta A (Fib-beta A)] analogous to compact plaques. In primary rat hippocampal culture, Fib-beta A was neurotoxic, whereas Am-beta A was not toxic. Fib-beta A caused significant loss of synapses in viable neurons, while Am-beta A had no effect on synapse number. The amyloid fibril-binding dye Congo red inhibited Fib-beta A neurotoxicity by inhibiting fibril formation or by binding to preformed fibrils. Congo red also inhibited the pancreatic islet cell toxicity of diabetes-associated amylin, another type of amyloid fibril. These results indicate that beta A neurotoxicity requires fibril formation. These findings and our previous demonstration that amylin fibrils are toxic suggest that a common cytopathic effect of amyloid fibrils may contribute to the pathogenesis of Alzheimer disease and other amyloidoses.

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The effect of synthetic Aβ might depend on the concentration of amyloid, the incubation time, and the presence of fibrillar or oligomeric amyloid.
“the effect of synthetic Aβ might depend on the concentration of amyloid, the incubation time, and the presence of fibrillar or oligomeric amyloid [41].”
From Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease (2021) · cites this paper as [41]
The Abstract reports that fibrillar Aβ was neurotoxic in primary rat hippocampal cultures, whereas amorphous Aβ was not, supporting a dependence on physical form. Our copy does not establish that the effect depends on amyloid concentration or incubation time, and it does not compare fibrils with oligomers. (LLM, conf=0.87)
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Authors: Lorenzo, A., & Yankner, B. A.
Affiliations: Harvard University (US)
Boston Children's Hospital (US)
ORCID: Lorenzo, A
Yankner, B A
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1994-12-06
Volume: 91
Issue: 25
Pages: 12243-12247
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.91.25.12243
PMC: PMC45413
OpenAlex: W1981570625
Cited by: 1,324
References: 5
Citations by year: 2026: 7 · 2025: 9 · 2024: 17 · 2023: 22 · 2022: 15 · 2021: 20 · 2020: 30 · 2019: 26 · 2018: 27 · 2017: 34 · 2016: 28 · 2015: 36 · 2014: 40 · 2013: 34 · 2012: 43
FWCI: 21.49
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: Alzheimer's Association
National Institutes of Health (5r29ag009229-05)
National Institute on Aging (AG09229)
National Institute of Neurological Disorders and Stroke (R01NS030352, NS30352)
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, neurotoxicity, amyloid fibril formation, Congo red, Alzheimer's disease, synaptic loss, hippocampal neurons, amylin, amyloid plaques, amyloidosis
MeSH terms: Amyloid, Animals, Cells, Cultured, Congo Red, Dose-Response Relationship, Drug, Hippocampus, Islets of Langerhans, Nerve Degeneration, Neurons, Neurotoxins, Structure-Activity Relationship, Synapses, Amyloid beta-Peptides, Rats, Islet Amyloid Polypeptide

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Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.

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