Tyrosine photophysics during the early stages of β-amyloid aggregation leading to Alzheimer's

We have monitored the formation of toxic β-amyloid oligomers leading to Alzheimer's disease by detecting changes in the fluorescence decay of intrinsic tyrosine. A new approach based on the non-Debye model of fluorescence kinetics resolves the complexity of the underlying photophysics. The gradual disappearance of nonmonotonic fluorescence decay rates, at the early stages of aggregation as larger, tighter-packed oligomers are formed, is interpreted in terms of tyrosine-peptide dielectric relaxation influencing the decay. The results demonstrate the potential for a new type of fluorescence lifetime sensing based on dual excited-state/dielectric relaxation, with application across a broad range of biological molecules. The results also reconcile previously conflicting models of protein intrinsic fluorescence decay based on rotamers or dielectric relaxation by illustrating conditions under which both are manifest

Inhibition of beta-amyloid aggregation by fluorescent dye labels

The fluorescence decay of beta-amyloid’s (Ab) intrinsic fluorophore tyrosine has been used for sensing the oligomer formation of dye-labelled Ab monomers and the results compared with previously studied oligomerization of the non-labelled Ab peptides. It has been demonstrated that two different sized, covalently bound probes 7-diethylaminocoumarin-3-carbonyl and Hilyte Fluor 488 (HLF), alter the rate and character of oligomerization to different extents. The ability of HLF to inhibit formation of highly ordered structures containing beta-sheets was also shown. The implications of our findings for using fluorescence methods in amyloidosis research are discussed and the advantages of this auto-fluorescence approach highlighted

Cu 2+ effects on beta-amyloid oligomerisation monitored by the fluorescence of intrinsic tyrosine

A non‐invasive intrinsic fluorescence sensing of the early stages of Alzheimer’s beta amyloid peptide aggregation in the presence of copper ions is reported. By using time‐resolved fluorescence techniques the formation of beta amyloid‐copper complexes and the accelerated peptide aggregation are demonstrated. The shifts in the emission spectral peaks indicate that the peptides exhibit different aggregation pathways than in the absence of copper