A spectroscopic marker for structural transitions associated with amyloid-β aggregation Academic Article uri icon

abstract

  • An amyloid aggregate evolves through a series of intermediates that have different secondary structures and intra- and intermolecular contacts. The structural parameters of these intermediates are important determinants of their toxicity. For example, the early oligomeric species of the amyloid-β (Aβ) peptide have been implicated as the most cytotoxic species in Alzheimer's disease but are difficult to identify because of their dynamic and transitory nature. Conventional aggregation monitors such as the fluorescent dye thioflavin T report on only the overall transition of the soluble species to the final amyloid fibrillar aggregated state. Here, we show that the fluorescent dye bis(triphenylphosphonium) tetraphenylethene (TPE-TPP) identifies at least three distinct aggregation intermediates of Aβ. Some atomic-level features of these intermediates are known from solid state nuclear magnetic resonance spectroscopy. Hence, the TPE-TPP fluorescence data may be interpreted in terms of these Aβ structural transitions. Steady state fluorescence and lifetime characteristics of TPE-TPP distinguish between the small oligomeric species (emission wavelength maximum, λmax = 465 nm; average fluorescence lifetime, τFl measured at 420 nm = 3.58 ± 0.04 ns), the intermediate species (λmax = 452 nm; τFl = 3.00 ± 0.03 ns), and the fibrils (λmax = 406 nm; τFl = 5.19 ± 0.08 ns). Thus, TPE-TPP provides a ready diagnostic for differentiating between the various, including the toxic, Aβ aggregates and potentially can be utilized to screen for amyloid aggregation inhibitors.

authors

  • Das, Anirban
  • Gupta, Ankur
  • Hong, Yuning
  • Carver, John A
  • Maiti, Sudipta

publication date

  • 2020