Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils

Petkova, Aneta T.; Leapman, Richard D.; Guo, Zhihong; Yau, Wai-Ming; Mattson, Mark P.; Tycko, Robert

doi:10.1126/science.1105850

Cited by 1,687Alzheimer's disease research and treatmentsPrion Diseases and Protein MisfoldingSupramolecular Self-Assembly in Materials

Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils

Petkova, Aneta T., Leapman, Richard D., Guo, Zhihong, Yau, Wai-Ming, Mattson, Mark P., Tycko, Robert·2005·Science

DOI 10.1126/science.1105850

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Abstract

Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue β-amyloid peptide of Alzheimer's disease (Aβ 1–40 ), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Aβ 1–40 fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials.

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Authors: Petkova, A. T., Leapman, R. D., Guo, Z., Yau, W.-M., Mattson, M. P., & Tycko, R.
Affiliations: National Institutes of Health (US)
Corresponding author: Tycko, Robert
ORCID: Leapman, Richard D.
Yau, Wai-Ming
Mattson, Mark P.
Tycko, Robert
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2005-01-14
Volume: 307
Issue: 5707
Pages: 262-265
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1105850
OpenAlex: W2004098528
Cited by: 1,687
References: 31
Citations by year: 2026: 34 · 2025: 43 · 2024: 45 · 2023: 57 · 2022: 47 · 2021: 72 · 2020: 67 · 2019: 74 · 2018: 92 · 2017: 84 · 2016: 93 · 2015: 73 · 2014: 93 · 2013: 114 · 2012: 102
FWCI: 57.13
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
Keywords: amyloid fibrils, beta-amyloid peptide, Aβ(1-40), Alzheimer's disease, fibril polymorphism, fibril morphology, self-propagation, amyloid toxicity, prion disease
MeSH terms: Animals, Cells, Cultured, Chemistry, Physical, Hippocampus, Humans, Hydrogen Bonding, Neurons, Peptide Fragments, Protein Conformation, Molecular Structure, Amyloid beta-Peptides, Protein Structure, Secondary, Microscopy, Atomic Force, Nuclear Magnetic Resonance, Biomolecular, Amino Acid Motifs, Microscopy, Electron, Transmission, Rats, Chemical Phenomena

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Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils

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