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Science 14 January 2005:
Vol. 307. no. 5707, pp. 262 - 265
DOI: 10.1126/science.1105850
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Reports

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

Aneta T. Petkova,1 Richard D. Leapman,2 Zhihong Guo,3 Wai-Ming Yau,1 Mark P. Mattson,3 Robert Tycko1*

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 ß-amyloid peptide of Alzheimer's disease (Aß1–40), 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 Aß1–40 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.

1 Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892–0520, USA.
2 Division of Bioengineering and Physical Science, Office of Research Services, NIH, Bethesda, MD 20892–5766, USA.
3 Laboratory of Neurosciences, National Institute of Aging, NIH, Baltimore, MD 21224–6825, USA.

* To whom correspondence should be addressed. E-mail: rt46d{at}nih.gov

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