Investigating New Applications of a Photoswitchable Fluorescent Norbornadiene as a Multifunctional Probe for Delineation of Amyloid Plaque Polymorphism
Journal article, 2023
Amyloid beta (Aβ) plaques are a major pathological hallmark of Alzheimer’s disease (AD) and constitute of structurally heterogenic entities (polymorphs) that have been implicated in the phenotypic heterogeneity of AD pathology and pathogenesis. Understanding amyloid aggregation has been a critical limiting factor to gain understanding of AD pathogenesis, ultimately reflected in that the underlying mechanism remains elusive. We identified a fluorescent probe in the form of a turn-off photoswitchable norbornadiene derivative (NBD1) with several microenvironment-sensitive properties that make it relevant for applications within advanced fluorescence imaging, for example, multifunctional imaging. We explored the application of NBD1 for in situ delineation of structurally heterogenic Aβ plaques in transgenic AD mouse models. NBD1 plaque imaging shows characteristic broader emission bands in the periphery and more narrow emission bands in the dense cores of mature cored plaques. Further, we demonstrate in situ photoisomerization of NBD1 to quadricyclane and thermal recovery in single plaques, which is relevant for applications within both functional and super-resolution imaging. This is the first time a norbornadiene photoswitch has been used as a probe for fluorescence imaging of Aβ plaque pathology in situ and that its spectroscopic and switching properties have been studied within the specific environment of senile Aβ plaques. These findings open the way toward new applications of NBD-based photoswitchable fluorescent probes for super-resolution or dual-color imaging and multifunctional microscopy of amyloid plaque heterogeneity. This could allow to visualize Aβ plaques with resolution beyond the diffraction limit, label different plaque types, and gain insights into their physicochemical composition.
Alzheimer’s disease (AD)
amyloid polymorphism
norbornadiene (NBD)
amyloid beta (Aβ)
fluorescence imaging
multifunctional probes
photoswitches
Author
Ambra Dreos
Instituto de Investigación Biomédica de Málaga (IBIMA)
University of Gothenburg
Junyue Ge
University of Gothenburg
Francisco Najera
University of Malaga
Instituto de Investigación Biomédica de Málaga (IBIMA)
Behabitu Ergette Tebikachew
Chalmers, Chemistry and Chemical Engineering, Energy and Material
E. Perez-Inestrosa
University of Malaga
Instituto de Investigación Biomédica de Málaga (IBIMA)
Kasper Moth-Poulsen
Catalan Institution for Research and Advanced Studies
Chalmers, Chemistry and Chemical Engineering, Applied Chemistry
Polytechnic University of Catalonia
Spanish National Research Council (CSIC)
Kaj Blennow
Sahlgrenska University Hospital
University of Gothenburg
Henrik Zetterberg
Hong Kong Center for Neurodegenerative Diseases
University College London (UCL)
University of Gothenburg
University of Wisconsin Madison
Sahlgrenska University Hospital
Jörg Hanrieder
University College London (UCL)
University of Gothenburg
ACS Sensors
23793694 (eISSN)
Vol. 8 4 1500-1509Subject Categories (SSIF 2011)
Atom and Molecular Physics and Optics
DOI
10.1021/acssensors.2c02496
PubMed
36946692