Alzheimer's Disease (AD), the most common form of dementia, is becoming one of the major healthcare challenges of this century.  The evolution of soluble amyloid-β (Aβ) to insoluble aggregates is implicated in the development of this AD. In the past decades, photoluminescent probes have shed light on the transition of Aβ monomers into oligomers and fibrils. We have particularly focused in photoluminescent metal complexes for studying amyloid proteins. We have found that metal dipyridophenazine complexes display a light switching effect when in the presence of Aβ aggregates. Recently, we reported the use of the anisotropy of Ru(II) polypyridyl complex as a way to study the formation of amyloid oligomers in real-time. As the size and concentration of aggregates increase, the anisotropy signal increases which can be used to monitor the formation of these elusive amyloid species. Out data shows immediate formation of Aβ oligomers that level off around 48 hours. In addition, we observed that the rate and amount of aggregates formed is temperature dependent. In addition,  we used the same Ru complex to study amyloid binding sites using photoluminescence lifetime. In contrast with previous light switching Ru dipyridophenazine complexes used to study amyloids, we chose Ru complexes that are always photoluminescent. This allowed the deconvolution of the different emission signals from using photoluminescence lifetime. In solution, the Ru complex presents a 435 ns monoexponential lifetime, while a biexponential lifetime with 435 ns and 1065 ns components is observed in the presence of Aβ fibrils. Our results shows that in contrast with previous studies, Aβ fibrils present at least two binding sites, with relatively similar dissociation constants, but different effects on the photophysics of the ruthenium probe.  This new information is shaping our understanding on how Aβ aggregates and on the kinds of binding pockets available on the surface of Aβ for molecular binding.

Understanding the aggregation and binding sites of amyloid nanoaggregates using photoluminescent ruthenium probes

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.