Gold nanorods plasmonic chirality allows detection and characterization of alpha-synuclein fibrils generated $in vitro$ and $in vivo$.

Alpha-synuclein ($\alpha$Syn) aggregates are found in Lewy bodies, key neuropathological hallmarks of Parkinson's disease (PD). Recently, it was shown that gold nanorods assume helical arrangements in the presence of human full length (fl) $\alpha$Syn fibrils, generating optical activity at the plasmon wavelengths. In this way, nanomolar concentrations of both fl and C-terminally truncated (1--120) $\alpha$Syn fibrils are detected through plasmonic circular dichroism (CD). We worked on fibrils generated $in vitro$ from human recombinant fl and (1--120) $\alpha$Syn and on fibril-enriched protein extracts produced from 1) neuroblastoma cells treated with $\alpha$Syn monomers either fl or (1--120) $\alpha$Syn protofibrils; 2) the striatum of mice that received the unilateral injection of adeno associated viral vectors overexpressing human fl $\alpha$Syn; 3) $post-mortem$ brains of PD patients at two different stages of PD. In all cases, characteristic bisignate CD signals were recorded, exhibiting wavelength shift from fl to (1--120) $\alpha$Syn fibrils. Also, sign reversal of the CD couplet was observed from $in vivo$ to $in vitro$ fibrils, supporting that chiroptical spectroscopies are sensitive to fibril handedness and different morphologies.