Detection and Imaging of Aβ1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues

Jun Zhang, Alexander Sandberg, Audun Konsmo, Xiongyu Wu, Sofie Nyström, K. Peter R. Nilsson, Peter Konradsson, Harry LeVine, Mikael Lindgren, Per Hammarström

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We revisited the Congo red analogue 2,5-bis(4′-hydroxy-3′-carboxy-styryl)benzene (X-34) to develop this highly fluorescent amyloid dye for imaging Alzheimer's disease (AD) pathology comprising Aβ and Tau fibrils. A selection of ligands with distinct optical properties were synthesized by replacing the central benzene unit of X-34, with other heterocyclic moieties. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of Aβ1-42 (13–300 nm Kd) and Tau (16–200 nm Kd) as well as selectivity towards the corresponding disease-associated protein aggregates in AD tissue. We observed that these ligands efficiently displaced X-34, but not Pittsburgh compound B (PiB) from recombinant Aβ1-42 amyloid fibrils, arguing for retained targeting of the Congo red type binding site. We foresee that the X-34 scaffold offers the possibility to develop novel high-affinity ligands for Aβ pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of Aβ fibrils.

Original languageEnglish
Pages (from-to)7210-7216
Number of pages7
JournalChemistry - A European Journal
Volume24
Issue number28
DOIs
StatePublished - May 17 2018

Bibliographical note

Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • Alzheimer's disease
  • amyloid ligands
  • dyes/pigments
  • fluorescence
  • microscopy

ASJC Scopus subject areas

  • General Chemistry
  • Catalysis
  • Organic Chemistry

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