CSF PrP-amyloid seeding predicts clinical onset in inherited prion disease

CSF RT-QuIC positivity in PRNP E200K mutation carriers predicts near-term clinical conversion, with first positive results appearing a median 2.0 years before symptoms.

• Why it matters: Proteopathic seeding is thought to precede neurodegeneration, but direct human evidence linking a measurable seeding signal to imminent symptom onset has been missing.
• What they did: Longitudinal CSF RT-QuIC data from 94 PRNP E200K carriers across international natural history cohorts were analyzed to test whether seeding status predicts conversion.
• The result: Among 11 who developed inherited prion disease, all had at least one positive RT-QuIC before onset, and positivity marked a markedly increased short-term conversion risk.

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