Propagating structure of Alzheimer's β-amyloid(10-35) is parallel β-sheet with residues in exact register

Tammie L.S. Benzinger, David M. Gregory, Timothy S. Burkoth, Hélène Miller-Auer, David G. Lynn, Robert E. Botto, Stephen C. Meredith

Research output: Contribution to journalArticlepeer-review

401 Scopus citations


The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa β-amyloid (Aβ) peptide. Crosslinking of Aβ peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated Aβ. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the Aβ peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated Aβ. Peptides containing a single carbonyl 13C label at Gln15, Lys16, Leu17, or Val18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Å. Analysis of these data establish that this central core of Aβ consists of a parallel β-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the Aβ fibril is a hydrogen-bonded, parallel β-sheet defining the long axis of the Aβ fibril propagation.

Original languageEnglish
Pages (from-to)13407-13412
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Nov 10 1998


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