Alzheimer's Disease is characterized histopathologically by the deposition of amyloid plaques, especially in areas of neuron loss.  The primary component of these plaques is a 39-43 amino acid peptide called $-amyloid (A$).  Specific interpeptide distance constraints are determined with dipolar recoupling NMR on fibrils prepared from a series of singly labeled peptides containing ¹³C-carbonyl-enriched amino acids, and skipping no more that three residues in the sequence. From these studies, we demonstrate that the peptide adopts the structure of an extended parallel $-sheet in-register at pH 7.4.  Analysis of NMR data indicates interstrand distances of 5.3 ± 0.3 Å (mean ± standard deviation) throughout the entire length of the peptide.  Intrastrand NMR constraints, obtained from peptides containing labels at two adjacent amino acids, confirm these findings.  Using peptides with ¹³C incorporated at the carbonyl position of adjacent amino acids, structural transitions from an "-helix to $-sheet were observed at residues 19 and 20, but using similar techniques, no evidence for a turn could be found in the putative turn region comprising residues 25-29.   SAXS and SANS were used to characterize long-range order.  Implications of this extended parallel organization for A$(10-35) for overall fibril formation, stability, local disorder, and morphology based upon specific amino acid contacts will be discussed.

Robert E. Botto is a chemist/spectroscopist at Argonne National Laboratory. He received his A.B. in Chemistry from Rutgers University and his M.S. and Ph.D. in Organic Chemistry from Michigan State University.

Robert has received several honors, including the Pacesetter Award, Argonne National Laboratory (1995); National Research Council Research Fellow, National Bureau of Standards (1979-81); NATO Grant Award (1977); Merit Teaching Award, Michigan State University (1973).

He has been a National Tour Speaker for the Society for Applied Spectroscopy, a co-organizer of the 5^th and 7^th Int'l Conferences on Magnetic Resonance Microscopy, session chairman of "Applications of NMR to Complex Systems," at the fall 1999 ACS National Meeting, symposium chairman on "Solid State NMR: Materials Imaging and Polymer Spectroscopy," at the 1995 Chemical Congress of Pacific Basin Societies, U.S. Editor, "Journal of Solid-State NMR", 1994-present, NMR Symposium chairman (1993) and co-chairman (1994) for the Rocky Mountain Conference, editor of the ACS Advances in Chemistry Series, "Techniques in Magnetic Resonance of Carbonaceous Solids", 1993, NMR Laboratory Director, Chemistry Division, 1990-1995.  Dr. Botto has several publications and is the co-editor and editor of a number of books on magnetic resonance.

Updated 11/4/04