Prion diseases are like a speeding freight train of neurodegenerative disorders, relentlessly progressing and inevitably leading to death. These diseases occur when a specific misfolded protein, called the prion protein, accumulates in the central nervous system. Diagnosing prion diseases is incredibly difficult because their symptoms overlap with other neurological disorders, making it challenging to pinpoint the exact cause. Currently, the only definitive diagnosis can be made through post-mortem brain examination. However, scientists have made significant progress in developing an innovative technique called Real-Time Quaking-Induced Conversion (RT-QuIC) to diagnose prion diseases while patients are still alive. Using an amplification strategy, RT-QuIC can detect the misfolded prion protein in cerebrospinal fluid and even in peripheral tissues with high sensitivity and specificity. This breakthrough has the potential to revolutionize the early and preclinical diagnosis of prion diseases, especially for individuals at genetic risk. By detecting the pathological prion protein before symptoms appear, clinicians can intervene earlier and potentially slow down disease progression. The future of diagnosing human prion diseases looks promising with the use of RT-QuIC! To learn more about this exciting research and its implications, dive into the full article.

Prion diseases are rapidly progressive, invariably fatal, transmissible neurodegenerative disorders associated with the accumulation of the amyloidogenic form of the prion protein in the central nervous system (CNS). In humans, prion diseases are highly heterogeneous both clinically and neuropathologically. Prion diseases are challenging to diagnose as many other neurologic disorders share the same symptoms, especially at clinical onset. Definitive diagnosis requires brain autopsy to identify the accumulation of the pathological prion protein, which is the only specific disease biomarker. Although brain post-mortem investigation remains the gold standard for diagnosis, antemortem clinical, instrumental, and laboratory tests showing variable sensitivities and specificity, being surrogate disease biomarkers, have been progressively introduced in clinical practice to reach a diagnosis. More recently, the ultrasensitive Real-Time Quaking-Induced Conversion (RT-QuIC) assay, exploiting, for the first time, the detection of misfolded prion protein through an amplification strategy, has highly improved the “in-vitam” diagnostic process, reaching in cerebrospinal fluid (CSF) and olfactory mucosa (OM) around 96% sensitivity and close to 100% specificity. RT-QuIC also improved the detection of the pathologic prion protein in several peripheral tissues, possibly even before the clinical onset of the disease. The latter aspect is of great interest for the early and even preclinical diagnosis in subjects at genetic risk of developing the disease, who will likely be the main target population in future clinical trials. This review presents an overview of the current knowledge and future perspectives on using RT-QuIC to diagnose human prion diseases.

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