Investigating New Applications of a Photoswitchable Fluorescent Norbornadiene as a Multifunctional Probe for Delineation of Amyloid Plaque Polymorphism
Artikel i vetenskaplig tidskrift, 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)
fluorescence imaging
Alzheimer’s disease (AD)
photoswitches
multifunctional probes
norbornadiene (NBD)
amyloid polymorphism
Författare
Ambra Dreos
Göteborgs universitet
Instituto de Investigación Biomédica de Málaga (IBIMA)
Junyue Ge
Göteborgs universitet
Francisco Najera
Universidad De Malaga
Instituto de Investigación Biomédica de Málaga (IBIMA)
Behabitu Ergette Tebikachew
Chalmers, Kemi och kemiteknik, Energi och material
E. Perez-Inestrosa
Universidad De Malaga
Instituto de Investigación Biomédica de Málaga (IBIMA)
Kasper Moth-Poulsen
Institucio Catalana de Recerca i Estudis Avancats
Universitat Politecnica de Catalunya
Chalmers, Kemi och kemiteknik, Tillämpad kemi
Consejo Superior de Investigaciones Científicas (CSIC)
Kaj Blennow
Sahlgrenska universitetssjukhuset
Göteborgs universitet
Henrik Zetterberg
Göteborgs universitet
Sahlgrenska universitetssjukhuset
University College London (UCL)
Hong Kong Center for Neurodegenerative Diseases
University of Wisconsin Madison
Jörg Hanrieder
Göteborgs universitet
University College London (UCL)
ACS Sensors
23793694 (eISSN)
Vol. 8 4 1500-1509Ämneskategorier (SSIF 2011)
Atom- och molekylfysik och optik
DOI
10.1021/acssensors.2c02496
PubMed
36946692