Mixing Aβ(1–40) and Aβ(1–42) peptides generates unique amyloid fibrils

Linda Cerofolini; Enrico Ravera; Sara Bologna; Thomas Wiglenda; Annett Böddrich; Bettina Purfürst; Iryna Benilova; Magdalena Korsak; Gianluca Gallo; Domenico Rizzo; Leonardo Gonnelli; Marco Fragai; Bart De Strooper; Erich E. Wanker; Claudio Luchinat

doi:10.1039/D0CC02463E

Mixing Aβ(1–40) and Aβ(1–42) peptides generates unique amyloid fibrils†

Linda Cerofolini,

^a Enrico Ravera,

^ab Sara Bologna,

^ab Thomas Wiglenda,

^c Annett Böddrich,

^c Bettina Purfürst,

^d Iryna Benilova,

‡^e Magdalena Korsak,§^f Gianluca Gallo,

¶^ab Domenico Rizzo,

^ab Leonardo Gonnelli,

^ab Marco Fragai,

^ab Bart De Strooper,

*^eg Erich E. Wanker

*^c and Claudio Luchinat

*^abf

Author affiliations

* Corresponding authors

^a Magnetic Resonance Center (CERM), University of Florence and Interuniversity Consortium for Magnetic Resonance of Metalloproteins (CIRMMP), Via L. Sacconi 6, Sesto Fiorentino (FI), Italy
E-mail: claudioluchinat@cerm.unifi.it

^b Department of Chemistry “Ugo Schiff”, University of Florence, Via della Lastruccia 3, Sesto Fiorentino (FI), Italy

^c Neuroproteomics, Max Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125 Berlin, Germany
E-mail: ewanker@mdc-berlin.de

^d Core Facility Electron Microscopy, Max-Delbrück Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125 Berlin, Germany

^e VIB Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium

^f Giotto Biotech S.R.L., Via Madonna del Piano 6, 50019 Sesto Fiorentino (FI), Italy

^g KULeuven, Department of Neurology, Herestraat 49, 3000 Leuven, Belgium
E-mail: bart.destrooper@kuleuven.vib.be

Abstract

Recent structural studies show distinct morphologies for the fibrils of Aβ(1–42) and Aβ(1–40), which are believed not to co-fibrillize. We describe here a novel, structurally-uniform 1 : 1 mixed fibrillar species, which differs from both pure fibrils. It forms preferentially even when Aβ(1–42) : Aβ(1–40) peptides are mixed in a non-stoichiometric ratio.

Chemical Communications

Mixing Aβ(1–40) and Aβ(1–42) peptides generates unique amyloid fibrils†

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Mixing Aβ(1–40) and Aβ(1–42) peptides generates unique amyloid fibrils

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