Alpha-synuclein seeds of Parkinson´s disease show high prion-exceeding resistance to steam sterilization.

Abstract Cerebral deposition of abnormally misfolded and aggregated alpha-synuclein (αSyn) is a neuropathological hallmark of Parkinson´s disease (PD). Pathologically aggregated αSyn species of PD (αSynPD) can act, in a 'prion-like' manner, as proteinaceous nuclei ('seeds') which are able of self-templated propagation. This has raised concerns that αSynPD seeds iatrogenically transmitted between humans may stimulate αSyn pathologies or clinically harmful effects in recipients. Effective decontamination when reprocessing medical devices could significantly counteract such risks. Steam sterilization at 134° C is recommended as an essential pathogen inactivation step in many reprocessing guidelines for medical devices and shows effectiveness also against prions, the self-propagating biological agents long thought to exhibit the highest resistance to steam sterilization. Therefore, we examined the reduction of αSynPD seeding activity in brain tissue homogenates from PD patients after steam sterilization at 134°C using a specifically adapted real-time quaking induced conversion assay (RT-QuIC). We detected titres of about 1010 50% seeding doses (SD50) per gram in non-steam sterilized caudate nucleus tissue of PD patients by endpoint-titration. Five minutes of steam sterilization reduced this titre by only 2.25 ± 0.15 decadic-logarithmic units, with an extension of the sterilization time to 90 minutes not causing additional inactivation. Our findings reveal αSynPD species as disease-associated biological agents the seeding activity of which has a higher resistance to steam sterilization than that of prions. The remarkable heat-resistance of αSynPD seeds calls for thoroughly validated cleaning and disinfection methods that reliably remove or inactivate possible contaminations of seeding-active αSyn aggregates when reprocessing medical devices.