Surface Modification of Ultrasonic Cavitation by Surfactants Improves Detection Sensitivity of α-Synuclein Amyloid Seeds.

ABSTRACT

The rapid amplification and sensitive detection of α-synuclein (αSyn) seeds is an efficient approach for the early diagnosis of Parkinson's disease. Ultrasonication stands out as a promising method for the rapid amplification of αSyn seeds because of its robust fibril fragmentation capability. However, ultrasonication also induces the primary nucleation of αSyn monomers, deteriorating the seed detection sensitivity by generating seed-independent fibrils. In this study, we show that an addition of surfactants to the αSyn monomer solution during αSyn seed detection under ultrasonication remarkably improves the detection sensitivity of the αSyn seeds by a factor of 100-1000. Chemical kinetic analysis reveals that these surfactants reduce the rate of primary nucleation while promoting the fragmentation of the αSyn fibrils under ultrasonication. These effects are attributed to the modification of the ultrasonic cavitation surface by the surfactants. Our study enhances the utility of ultrasonication in clinical assays targeting αSyn seeds as the Parkinson's disease biomarker.