Three-Way Clustering of RT-QuIC for Prion Disease Diagnosis

Prion diseases, such as Creutzfeldt–Jakob disease (CJD), are rare, invariably fatal, and rapidly progressive neurodegenerative disorders caused by the accumulation of misfolded prion protein (PrPSc) in the central nervous system. Their diagnosis is challenging due to clinical heterogeneity and symptom overlap with other neurological conditions (including treatment responsive mimics). While brain autopsy remains the gold standard, Real-Time Quaking-Induced Conversion (RT-QuIC) has revolutionized antemortem detection by identifying PrPSc with near-perfect specificity and high sensitivity. RT-QuIC works by amplifying PrPSc’s seeding activity, primarily assessing lag-phase and maximum intensity for improved diagnostic precision. To enhance its clinical applicability, we will apply a three-way data clustering approach to RT-QuIC results, aiming to classify disease subtypes and improve diagnostic accuracy by considering all the fluorescence dis- tribution and not only the two most significant kinetic parameters of the reaction, that is the lag-phase and the maximum intensity (peak of fluorescent signal). This method will allow for a refined interpretation of RT-QuIC parameters, potentially distinguishing prion disease variants and optimizing early detection strategies.