Application of protein misfolding amplification techniques in prion diseases

Prion diseases (PrDs) are fatal neurodegenerative disorders caused by the misfolding and aggregation of pathogenic prion protein (PrPSc). Traditional diagnostic methods have limited sensitivity and specificity, often requiring confirmation in the late stages or postmortem. In recent years, protein misfolding amplification techniques, including protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC), have achieved significant breakthroughs, enabling ultrasensitive detection of PrPSc with detection limits as low as the attogram level. These methods greatly enhance diagnostic accuracy and offer the potential for early and non-invasive detection of PrDs. Their success has extended to other seeding-based neurodegenerative diseases, such as Parkinson’s disease (PD), providing a powerful tool for early diagnosis, molecular pathology research, and clinical translation. Beyond diagnosis, these techniques play a crucial role in investigating strain characteristics and pathology, as well as in screening potential drugs for PrDs. They are also applied in research of public health security, including variant Creutzfeldt-Jakob disease (vCJD) surveillance, cross-species risk assessment, and environmental contamination monitoring and optimization of decontamination strategies. With exceptional sensitivity and specificity, these techniques are revolutionizing the landscape of neurodegenerative disease detection and intervention.