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.
†Photophysics Group, Centre for Molecular Nanometrology, Department of Physics, Scottish Universities Physics Alliance, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG, United Kingdom.
Olaf J
OJ
Rolinski
†Photophysics Group, Centre for Molecular Nanometrology, Department of Physics, Scottish Universities Physics Alliance, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG, United Kingdom.
Thorben
T
Wellbrock
†Photophysics Group, Centre for Molecular Nanometrology, Department of Physics, Scottish Universities Physics Alliance, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG, United Kingdom.
David J S
DJ
Birch
‡School of Mathematics and Statistics, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Vladislav
V
Vyshemirsky
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D012709:Serum Albumin; D014443:Tyrosine
Alzheimer’s disease; non-Debye kinetics; protein fluorescence; tyrosine; β-amyloid aggregation