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.

amyloid beta (Aβ)

multifunctional probes

amyloid polymorphism

fluorescence imaging

Alzheimer’s disease (AD)

norbornadiene (NBD)



Ambra Dreos

University of Gothenburg

Instituto de Investigación Biomédica de Málaga (IBIMA)

Junyue Ge

University of Gothenburg

Francisco Najera

Instituto de Investigación Biomédica de Málaga (IBIMA)

University of Malaga

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

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Institute of Material Science of Barcelona (ICMAB)

Catalan Institution for Research and Advanced Studies

Polytechnic University of Catalonia

Kaj Blennow

University of Gothenburg

Sahlgrenska University Hospital

Henrik Zetterberg

University College London (UCL)

University of Gothenburg

Sahlgrenska University Hospital

Hong Kong Center for Neurodegenerative Diseases

University of Wisconsin Madison

Jörg Hanrieder

University College London (UCL)

University of Gothenburg

ACS Sensors

23793694 (eISSN)

Vol. 8 4 1500-1509

Subject Categories

Atom and Molecular Physics and Optics





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