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Self-Propagating, Molecular-Level Polymorphism in Alzheimer's [beta]-Amyloid Fibrils

Petkova, Aneta T., Leapman, Richard D., Guo, Zhihong, Yau, Wai-Ming, Mattson, Mark P., Tycko, Robert
Science 2005 v.307 no.5707 pp. 262-265
Alzheimer disease, amyloid, cell culture, chemical structure, electron microscopy, nanomaterials, neurons, nuclear magnetic resonance spectroscopy, prion diseases
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 [beta]-amyloid peptide of Alzheimer's disease (A[beta]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 A[beta]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.