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Significance: This contribution reports on the application of gold nanorods to the detection of amyloids in Parkinson’s and prion diseases. We found that gold nanorods show no interaction with monomeric proteins but adsorb onto helical protein fibrils. Chiral amyloid templates induce helical arrangement of nanorods, giving rise to intense optical activity at the plasmon resonance wavelengths. This report shows the use of protein fibrils as templates for chiral nanoparticle assembly and development of a biodetection technique. We show this effect on a model recombinant protein, α-synuclein (involved in Parkinson’s disease), using CD, cryogenic transmission EM tomography, and theoretical simulations supporting the experimental findings. We additionally show application to identify patients with Parkinson’s disease from human brain homogenates.

Prions are the unconventional infectious agents responsible for transmissible spongiform encephalopathies, which appear to be composed mainly or exclusively of the misfolded prion protein (PrPSc). Prion replication involves the conversion of the normal prion protein (PrPC) into the misfolded isoform, catalyzed by tiny quantities of PrPSc present in the infectious material. We have recently developed the protein misfolding cyclic amplification (PMCA) technology to sustain the autocatalytic replication of infectious prions in vitro. Here we show that PMCA enables the specific and reproducible amplification of exceptionally minute quantities of PrPSc. Indeed, after seven rounds of PMCA, we were able to generate large amounts of PrPSc starting from a 1x10(-12) dilution of scrapie hamster brain, which contains the equivalent of approximately 26 molecules of protein monomers. According to recent data, this quantity is similar to the minimum number of molecules present in a single particle of infectious PrPSc, indicating that PMCA may enable detection of as little as one oligomeric PrPSc infectious particle. Interestingly, the in vitro generated PrPSc was infectious when injected in wild-type hamsters, producing a disease identical to the one generated by inoculation of the brain infectious material. The unprecedented amplification efficiency of PMCA leads to a several billion-fold increase of sensitivity for PrPSc detection as compared with standard tests used to screen prion-infected cattle and at least 4000 times more sensitivity than the animal bioassay. Therefore, PMCA offers great promise for the development of highly sensitive, specific, and early diagnosis of transmissible spongiform encephalopathy and to further understand the molecular basis of prion propagation.