CSF RT-QuIC (second generation)

Key facts

• Sensitivity 90.3 percent and specificity 98.5 percent at the US national center; a positive result carries over 98 percent likelihood of prion disease.
• Six-laboratory blinded ring trial: 98 to 100 percent concordance.
• Reviews report about 96 percent sensitivity and close to 100 percent specificity in CSF and olfactory mucosa; the Danish reference centre reports sensitivity above 90 percent and specificity 100 percent.
• In people at genetic risk who later converted, CSF RT-QuIC turned positive 1 year (E200K V/V) and 2.5 to 3.1 years (M/V) before onset.
• Limits: Reduced sensitivity for some genetic subtypes; a negative result needs interpretation with total tau; needs frozen sample and dry-ice shipment at some labs; not a predictive test for healthy carriers who are years from onset.
• What it asks of the person: Lumbar puncture; sample shipped frozen (US center: -20 C or colder, dry ice).
• Genetic subtypes differ: in an early study of 56 genetic prion disease CSF samples sensitivity was 78 percent for GSS (P102L), 87 percent for gCJD E200K, 100 percent for FFI (D178N) and 100 percent for V203I (assay generation not read).
• A Dutch national guideline reports RT-QuIC sensitivity 91.6 percent and specificity 100 percent and considers repeating RT-QuIC after four to six weeks if suspicion persists despite a negative result.

Timeline

1. 2026Death of RT-QuIC pioneer Byron Caughey.
2. 2026Evidence read for this dossier.