A fluorescent molecular imaging probe with selectivity for soluble tau aggregated protein

Yanyan Zhao, Ole Tietz, Wei Li Kuan, Abdul K. Haji-Dheere, Stephen Thompson, Benjamin Vallin, Elisabetta Ronchi, Gergely Tóth, David Klenerman, Franklin I. Aigbirhio*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
24 Downloads (Pure)

Abstract

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, pTP-TFE for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Our results have shown pTP-TFE to be selective for early forms of soluble tau aggregates, with high affinity of dissociation constants (Kd) = 66 nM, and tenfold selectivity over mature tau fibrils. Furthermore, we found that pTP-TFE is selective for tau over Aβ aggregates and had good cell permeability. This selectivity of pTP-TFE towards early forms of aggregated tau protein ex vivo was also supported with studies on human brain tissue containing tau and Aβ pathology. To the best of our knowledge, this is the first fluorescent molecule to be reported to have this form of selectivity profile, which suggests that pTP-TFE is a unique probe candidate for imaging-based detection of early stages of Alzheimer's disease and other tauopathies.

Original languageEnglish
Pages (from-to)4773-4778
Number of pages6
JournalChemical Science
Volume11
Issue number18
DOIs
Publication statusPublished - 14 May 2020
Externally publishedYes

Bibliographical note

Copyright the Royal Society of Chemistry 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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