Molecular Structures of Amyloid Fibrils in Alzheimer's Disease: Insights from Solid State NMR

ABSTRACT: Alzheimer's disease and related human diseases result from the aberrant aggregation of peptides and proteins into amyloid fibrils and related supramolecular assemblies.  The inherently insoluble and noncrystalline nature of amyloid fibrils has impeded the development of a molecular level structural understanding of amyloid formation.  I will describe work from my lab over the past 12 years in which we have shown that solid state nuclear magnetic resonance (NMR) methods, supplemented by electron microscopy, can be used to develop detailed molecular structural models for amyloid fibrils, especially fibrils formed by the beta-amyloid peptide that is associated with Alzheimer's disease.  Topics to be presented include the molecular structural basis for self-propagating amyloid polymorphisms, the nature of generic structural features in amyloid fibrils, the discovery and characterization of a structurally novel, metastable form of beta-amyloid fibrils, and initial progress towards the identification of amyloid fibril structures that develop in human brain tissue.

ABOUT THE SPEAKER: About the speaker: Tycko obtained his Ph.D. from Berkeley and has been at the NIH, Bethesda, since 1998. He has made significant contributions to the methods development in NMR and applications to biomolecules. Some of his research interests are: structural studies of amyloid fibrils, protein folding, membrane proteins, and optical pumping and dynamic nuclear polarisation solid-state NMR.  He was also involved with the characterisation by NMR of the electronic and dynamical properties of fullerenes and superconducting alkali fullerides and the initial demonstration of the effects of geometric quantum phases on magnetic resonance spectra.  Dr. Tycko received the American Physical Society's Earle K. Plyler Prize for Molecular Spectroscopy in 2005, the Chemical Society of Washington’s Hillebrand Prize in 2007, and NIH Director’s Award in 2001. He has been a distinguished lecturer in many conferences and is a fellow of the American Physical Society. This colloquium is part of the International Year of Chemistry progamme.