Recently, fluorescence-like emission was reported for synthetic amyloid-like structures of peptides derived from elastin and crystalline proteins^1-3. The structures studied were devoid of aromatic residues and extrinsic fluorescent labels, and consist of a high proportion of β-sheets. Authors of the reports hypothesized that the fluorescence-like emission could be due to electron delocalization via hydrogen bonds in the cross β-sheet structure that makes these low-energy electronic transitions possible. Based on this hypothesis, the authors proposed that amyloid fibrils could also exhibit intrinsic fluorescence. These reports did not, however, include fluorescence measurements of bona fide amyloid structures. Furthermore, a lack of time-resolved fluorescence measurements raises the possibility of artefacts due to inelastic scattering.

Here we show conclusively that amyloids formed by disease-relevant human polypeptides also exhibit intrinsic fluorescence. We report in detail on the evolution of photophysical properties during aggregation of the amyloid-β peptides and the amyloidogenic proteins tau and lysozyme, all of which are from the human genome and associated with protein misfolding diseases, and show that these polypeptides acquire intrinsic fluorescence signatures in the visible range upon aggregation. We use spectrum- and time-resolved fluorescence detection and imaging and conclude that the observed fluorescence is a generic property of amyloid structures with a characteristic lifetime for each polypeptide investigated. Intrinsic fluorescence was also detected from a fragment of amyloid-β(1-42) devoid of aromatics, amyloid-β(33-42). The result suggests that the phenomenon is not mediated by the presence of aromatic side chains in the amyloid structure. This is not consistent with a previous report that chemical modifications of aromatic residues in polypeptides occur during amyloid formation and lead to the formation of an intrinsic chromophore, like that of GFP⁴. Rather, our results support previous suggestions that electron delocalization via hydrogen bonds in the cross β-sheet structure, and extend the validity to disease-relevant amyloid fibrils.