Advancing Prion Diagnostics: RT-QuIC Applications in Peripheral Tissues

Prion diseases (PrDs) are fatal neurodegenerative disorders characterized by the accumulation of misfolded prion protein (PrPSc) in the central nervous system (CNS). This pathological isoform of the cellular prion protein drives disease pathogenesis through its unique ability to propagate itself via a template-directed misfolding mechanism. The definite diagnosis of PrDs relies on the detection of PrPSc in the CNS by invasive procedures or postmortem examination, limiting early detection and antemortem diagnostic investigations. Real-time quaking-induced conversion (RT-QuIC) has emerged as a revolutionary diagnostic tool, allowing ultrasensitive detection of PrPSc in cerebrospinal fluid (CSF) and other easily accessible tissues, including the olfactory mucosa, skin, and, more recently, tears. This assay exploits the autocatalytic amplification of misfolded prions, providing high sensitivity and specificity in the detection of peripheral PrPSc. This chapter explores the advancements and applications of RT-QuIC in diagnosing human PrDs.