Detection and Imaging of Aβ1‐42 and Tau Fibrils by Redesigned Fluorescent X‐34 Analogues. Issue 28 (26th April 2018)

• Record Type: Journal Article
• Authors: Zhang, Jun; Sandberg, Alexander; Konsmo, Audun; Wu, Xiongyu; Nyström, Sofie; Nilsson, K. Peter R.; Konradsson, Peter; LeVine, Harry; Lindgren, Mikael; Hammarström, Per
• Is Part Of: Chemistry. Volume 24:Issue 28(2018)
• Page Start: 7210
• Page End: 7216
• Publication Date: 2018-04-26
• Subjects: Alzheimer's disease -- amyloid ligands -- dyes/pigments -- fluorescence -- microscopy; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201800501
• Languages: English
• ISSNs: 0947-6539

Abstract

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 K d ) and Tau (16–200 nm K d ) 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. Abstract : New dyes from old : Four new fluorescent amyloid ligands based on the 2, 5‐bis(4′‐hydroxy‐3′‐carboxystyryl)benzene (X‐34) scaffold with new optical properties are reported (see figure).